血浆铁蛋白，铁代谢关键基因及其交互作用与冠心病的相关性
|
摘要
虽然铁是人体代谢必需的微量元素,但过量的铁参与很多病理过程,包括冠心病(Coronary Heart Disease, CHD)的发生和发展。病理学和动物学实验均证实铁负荷水平与冠心病发生有关,流行病学研究却得到了矛盾结果,这可能与未考虑机体铁代谢的遗传背景有关。我们将采用1：1病例—对照配对研究,选取1334对冠心病病例和对照为研究对象,用荧光定量PCR仪对铁代谢通路中的关键蛋白质HFE (Hemochromatosis, HFE)和转铁蛋白受体2 (transferrin receptor 2, TFR2)进行基因分型,酶联免疫吸附法(enzyme linked immunosorbent assay, ELISA)检测血浆铁蛋白,反映机体铁负荷水平；运用Logistic回归研究铁蛋白水平与HFE和TFR2基因的交互作用,以及HFE和TFR2基因多态性在冠心病发生中的主效应和基因一基因交互作用,探讨冠心病发生的分子机制。我们的研究有助于阐明铁负荷水平与冠心病的关系和冠心病可能的分子机制；并对促进冠心病患者早期筛检和个体化干预方案建立具有重要现实意义。
第一部分血浆铁蛋白、HFE基因多态性与冠心病相关性的研究
目的：病理学和动物学实验均证实铁负荷水平与冠心病发生和发展有关,流行病学研究却得到了矛盾结果,HFE基因是遗传性血色素沉着症候选基因,有研究证实与血浆铁负荷相关,我们将用病例—对照研究的方法在中国汉族人群中探讨HFE基因多态性、血浆铁蛋白与冠心病的相关性。
方法：采用病例—对照研究,选取1334个冠心病病人及1334个与其性别、年龄(±1)匹配的对照,使用ELISA测量血浆铁蛋白水平和血浆Hepcidin水平,Taqman-MGB探针检测HFE单核苷酸多态性(Single nucleotide polymorphism, SNP)。
结果：病例组中血浆铁蛋白水平明显高于对照组(197.9 ug/L [2.7 to 932.9 ug/L] vs 179.9 ug/L [21.1 to 878.2 ug/L], P=0.028),四分位危险度(oddds ratios, ORs)分别为1.0(参照),0.93(0.76-1.13),1.23(1.02.1.48)(P=0.028)。对冠心病危险因素进行校正后,病例组和对照组的ORs无显著性差异。在HFE基因rs9366637中,与TT型等位基因相比,携带C等位基因的患冠心病的危险度增加(TC的OR=1.35,CC的OR=1.76；P≤0.001),对冠心病危险因素进行校正后,结果无改变。rs9366637不同基因型之间的血浆铁蛋白水平和血浆Hepcidin水平差异无统计学意义(P=0.52)。
结论：血浆铁蛋白与冠心病风险无统计学差异,在中国汉族人群中HFE基因SNP rs9366637携带C等位基因的患冠心病的危险度增加,rs9366637不同基因型之间的血浆铁蛋白水平和血浆Hepcidin水平差异无统计学意义。
第二部分血浆铁蛋白、TFR2基因多态性与冠心病相关性的研究
目的：TFR2是一种铁转运和铁稳态调节蛋白,TFR2的突变可导致遗传性血色病Ⅲ型的发生,有研究证实TFR2与铁转运及铁负荷相关。我们将用病例—对照研究的方法在中国汉族人群中探讨TFR2基因多态性、血浆铁蛋白与冠心病的相关性。
方法：采用病例一对照研究,选取1334个冠心病病人及1334个与其性别、年龄(±1)匹配的对照,使用ELISA测量血浆铁蛋白水平和血浆Hepcidin水平,Taqman—MGB探针检测TFR2基因上SNPs rs7385804及rs2075673的基因分型。
结果：TFR2基因上SNPs rs7385804及rs2075673的基因型频率在冠心病组和对照组之间无显著性差异,对年龄、性别、吸烟、饮酒、高血压及冠心病家族史等冠心病危险因素进行校正后,未发现统计学差异(P>0.05),rs7385804及rs2075673不同基因型的血浆铁蛋白水平和Hepcidin水平无显著差异(P>0.05)。
结论：TFR2基因rs7385804及rs2075673多态性与冠心病风险无统计学意义,并且不同基因型的血浆铁蛋白水平和Hepcidin水平无显著差异。
第三部分HFE与TFR2基因—基因交互作用在冠心病中的作用
目的：对HFE及TFR2基因上共5个SNPs位点进行基因一基因的交互作用进行探讨,以明确HFE及TFR2基因交互作用与冠心病危险性的相关性。
方法：我们采用非条件Logistic回归分析模型,通过似然比检验,探讨HFE及TFR2基因上共5个SNPs位点的基因—基因交互作用。
结果：我们研究结果未发现HFE和TFR2基因5个SNPs位点间存在交互作用,对冠心病传统危险因素如吸烟、饮酒、年龄、性别、冠心病家族病史等进行校正后,结果无改变,各基因位点间均未发现交互作用(P>0.05)。
结论：我们未发现HFE与TFR2之间存在基因—基因交互作用,并且此交互作用与冠心病的危险性无统计学意义。
Although iron plays an important role in cell growth and division, an excess of iron can increase production of free radicals and cause tissue damage, which might participate in the etiology and progression of cardiovascular disease. Many phathology and animal studies have demonstrated this relationship, but some epidemiological studies yielded contradicting results. This might be due to the different population, different study design, and different sample size. We conducted a case-control study which composed of 1,334 case patients and 1,334 age- and sex- frequency matched controls to explore the associations between plasma ferritin levels, polymorphisms of key genes in iron metabolism and CHD.We used ELISA to detect the plasma ferritin levels and PCR to determine the genotypes of genes. And Logistic regression model was used to evaluated the associations between genotypes, plasma ferritin levels and CHD.
Background-- The association between body iron stores and coronary heart disease (CHD) was inconsistent. We sought to explore this association in Chinese Han population and further examine the association of the variations in hemochromatosis(HFE) gene and CHD risk.
Methods-- We conducted a case-control study including 1,334 CHD patients and 1,334 age- and sex- frequency matched controls. The plasma ferritin levels were measured by enzyme linked immunosorbent assay. Genotypes of the tagging single nucleotide polymorphisms (tagSNPs) were determined by TaqMan SNP allelic discrimination.
Results-- The plasma ferritin levels in CHD cases (197.9 ug/L [2.7 to 932.9 ug/L]) were higher than those in controls (179.9 ug/L [21.1 to 878.2 ug/L]; P=0.028). The odds ratios (ORs) across the tertiles of plasma ferritin levels were 1.0 (reference),0.93 (0.76-1.13), and 1.23 (1.02-1.48; P for trend=0.028). Adjustment for the traditional risk factors attenuated the associations to null (P for trend=0.22). Compared with the TT genotype of tagSNP rs9366637, subjects with C allele had higher risk of CHD (OR=1.35 for TC and 1.76 for CC;P=0.001 and<0.001 respectively). After adjustment for the conventional risk factors the results remained unchanged. We did not find significantly different plasma ferritin levels and Hepcidin levels among different genotypes of rs9366637 (P=0.52).
Conclusions--The plasma ferritin levels were not significantly associated with CHD risk. However, the SNP rs9366637 in HFE gene was associated with higher CHD risk in Chinese Han population, and there were not significantly different plasma ferritin levels and Hepcidin levels among different genotypes of rs9366637. The underlie mechanism remained to be elucidated in further studies.
Background--TFR2 is a homologue of the type transferring receptor 1 (TFR1), it may participate in cellular iron overload. We sought to reveal the associations of plasma ferritin, polymorphisms of TFR2 and CHD in Chinese Han population.
Methods--We recruited 1,334 CHD patients and 1,334 age- and sex- frequency matched controls to perform a case-control study. The plasma ferritin levels and Hepcidin levels were measured by ELISA. TaqMan SNP allelic discrimination was used to examine genotypes of the tagSNPs of TFR2.
Results-- We did not find any significant association between genotypes of TFR2 (including rs2075674 and rs7385804) and the risk of CHD (OR=1.04(0.86-1.25) for CT; OR=0.78(0.49-1.25) for TT of rs2075674 and OR=0.94(0.79-1.12) for AC; OR=1.15 (0.87-1.52) for CC of rs7385804, respectively). After adjustment for the conventional risk factors of CHD such as smoking, age, gender, history of hypertension and family history of CHD, the results did not alter. And we also did not find significantly different plasma ferritin levels and Hepcidin levels among different genotypes of rs2075674 and rs7385804 (P>0.05).
Conclusions-- The SNPs rs2075674 and rs7385804 in TFR2 gene were not associated with higher CHD risk in Chinese Han population and there were not significantly different plasma ferritin levels and Hepcidin levels among different genotypes of rs2075674 and rs7385804. The mechanism remained to be explored in further studies.
Objective:To explore the gene-gene interaction of HFE and TFR2 on CHD.
Method:We used unconditional Logistic regression model and likehood test to evaluate the gene-gene interaction of HFE and TFR2.
Results:We found there were not interactions between the SNPs of HFE and TFR2, after adjustment for the conventional risk factors such as smoking, drinking, age, gender and family history of CHD, the results did not change, we did not find any significant associations between gene-gene interaction of HFE and TFR2 and CHD (P>0.05).
Conclusion:There were not significant associations between gene-gene interaction of HFE and TFR2 and CHD.
第一部分血浆铁蛋白、HFE基因多态性与冠心病相关性的研究
目的：病理学和动物学实验均证实铁负荷水平与冠心病发生和发展有关,流行病学研究却得到了矛盾结果,HFE基因是遗传性血色素沉着症候选基因,有研究证实与血浆铁负荷相关,我们将用病例—对照研究的方法在中国汉族人群中探讨HFE基因多态性、血浆铁蛋白与冠心病的相关性。
方法：采用病例—对照研究,选取1334个冠心病病人及1334个与其性别、年龄(±1)匹配的对照,使用ELISA测量血浆铁蛋白水平和血浆Hepcidin水平,Taqman-MGB探针检测HFE单核苷酸多态性(Single nucleotide polymorphism, SNP)。
结果：病例组中血浆铁蛋白水平明显高于对照组(197.9 ug/L [2.7 to 932.9 ug/L] vs 179.9 ug/L [21.1 to 878.2 ug/L], P=0.028),四分位危险度(oddds ratios, ORs)分别为1.0(参照),0.93(0.76-1.13),1.23(1.02.1.48)(P=0.028)。对冠心病危险因素进行校正后,病例组和对照组的ORs无显著性差异。在HFE基因rs9366637中,与TT型等位基因相比,携带C等位基因的患冠心病的危险度增加(TC的OR=1.35,CC的OR=1.76；P≤0.001),对冠心病危险因素进行校正后,结果无改变。rs9366637不同基因型之间的血浆铁蛋白水平和血浆Hepcidin水平差异无统计学意义(P=0.52)。
结论：血浆铁蛋白与冠心病风险无统计学差异,在中国汉族人群中HFE基因SNP rs9366637携带C等位基因的患冠心病的危险度增加,rs9366637不同基因型之间的血浆铁蛋白水平和血浆Hepcidin水平差异无统计学意义。
第二部分血浆铁蛋白、TFR2基因多态性与冠心病相关性的研究
目的：TFR2是一种铁转运和铁稳态调节蛋白,TFR2的突变可导致遗传性血色病Ⅲ型的发生,有研究证实TFR2与铁转运及铁负荷相关。我们将用病例—对照研究的方法在中国汉族人群中探讨TFR2基因多态性、血浆铁蛋白与冠心病的相关性。
方法：采用病例一对照研究,选取1334个冠心病病人及1334个与其性别、年龄(±1)匹配的对照,使用ELISA测量血浆铁蛋白水平和血浆Hepcidin水平,Taqman—MGB探针检测TFR2基因上SNPs rs7385804及rs2075673的基因分型。
结果：TFR2基因上SNPs rs7385804及rs2075673的基因型频率在冠心病组和对照组之间无显著性差异,对年龄、性别、吸烟、饮酒、高血压及冠心病家族史等冠心病危险因素进行校正后,未发现统计学差异(P>0.05),rs7385804及rs2075673不同基因型的血浆铁蛋白水平和Hepcidin水平无显著差异(P>0.05)。
结论：TFR2基因rs7385804及rs2075673多态性与冠心病风险无统计学意义,并且不同基因型的血浆铁蛋白水平和Hepcidin水平无显著差异。
第三部分HFE与TFR2基因—基因交互作用在冠心病中的作用
目的：对HFE及TFR2基因上共5个SNPs位点进行基因一基因的交互作用进行探讨,以明确HFE及TFR2基因交互作用与冠心病危险性的相关性。
方法：我们采用非条件Logistic回归分析模型,通过似然比检验,探讨HFE及TFR2基因上共5个SNPs位点的基因—基因交互作用。
结果：我们研究结果未发现HFE和TFR2基因5个SNPs位点间存在交互作用,对冠心病传统危险因素如吸烟、饮酒、年龄、性别、冠心病家族病史等进行校正后,结果无改变,各基因位点间均未发现交互作用(P>0.05)。
结论：我们未发现HFE与TFR2之间存在基因—基因交互作用,并且此交互作用与冠心病的危险性无统计学意义。
Although iron plays an important role in cell growth and division, an excess of iron can increase production of free radicals and cause tissue damage, which might participate in the etiology and progression of cardiovascular disease. Many phathology and animal studies have demonstrated this relationship, but some epidemiological studies yielded contradicting results. This might be due to the different population, different study design, and different sample size. We conducted a case-control study which composed of 1,334 case patients and 1,334 age- and sex- frequency matched controls to explore the associations between plasma ferritin levels, polymorphisms of key genes in iron metabolism and CHD.We used ELISA to detect the plasma ferritin levels and PCR to determine the genotypes of genes. And Logistic regression model was used to evaluated the associations between genotypes, plasma ferritin levels and CHD.
Background-- The association between body iron stores and coronary heart disease (CHD) was inconsistent. We sought to explore this association in Chinese Han population and further examine the association of the variations in hemochromatosis(HFE) gene and CHD risk.
Methods-- We conducted a case-control study including 1,334 CHD patients and 1,334 age- and sex- frequency matched controls. The plasma ferritin levels were measured by enzyme linked immunosorbent assay. Genotypes of the tagging single nucleotide polymorphisms (tagSNPs) were determined by TaqMan SNP allelic discrimination.
Results-- The plasma ferritin levels in CHD cases (197.9 ug/L [2.7 to 932.9 ug/L]) were higher than those in controls (179.9 ug/L [21.1 to 878.2 ug/L]; P=0.028). The odds ratios (ORs) across the tertiles of plasma ferritin levels were 1.0 (reference),0.93 (0.76-1.13), and 1.23 (1.02-1.48; P for trend=0.028). Adjustment for the traditional risk factors attenuated the associations to null (P for trend=0.22). Compared with the TT genotype of tagSNP rs9366637, subjects with C allele had higher risk of CHD (OR=1.35 for TC and 1.76 for CC;P=0.001 and<0.001 respectively). After adjustment for the conventional risk factors the results remained unchanged. We did not find significantly different plasma ferritin levels and Hepcidin levels among different genotypes of rs9366637 (P=0.52).
Conclusions--The plasma ferritin levels were not significantly associated with CHD risk. However, the SNP rs9366637 in HFE gene was associated with higher CHD risk in Chinese Han population, and there were not significantly different plasma ferritin levels and Hepcidin levels among different genotypes of rs9366637. The underlie mechanism remained to be elucidated in further studies.
Background--TFR2 is a homologue of the type transferring receptor 1 (TFR1), it may participate in cellular iron overload. We sought to reveal the associations of plasma ferritin, polymorphisms of TFR2 and CHD in Chinese Han population.
Methods--We recruited 1,334 CHD patients and 1,334 age- and sex- frequency matched controls to perform a case-control study. The plasma ferritin levels and Hepcidin levels were measured by ELISA. TaqMan SNP allelic discrimination was used to examine genotypes of the tagSNPs of TFR2.
Results-- We did not find any significant association between genotypes of TFR2 (including rs2075674 and rs7385804) and the risk of CHD (OR=1.04(0.86-1.25) for CT; OR=0.78(0.49-1.25) for TT of rs2075674 and OR=0.94(0.79-1.12) for AC; OR=1.15 (0.87-1.52) for CC of rs7385804, respectively). After adjustment for the conventional risk factors of CHD such as smoking, age, gender, history of hypertension and family history of CHD, the results did not alter. And we also did not find significantly different plasma ferritin levels and Hepcidin levels among different genotypes of rs2075674 and rs7385804 (P>0.05).
Conclusions-- The SNPs rs2075674 and rs7385804 in TFR2 gene were not associated with higher CHD risk in Chinese Han population and there were not significantly different plasma ferritin levels and Hepcidin levels among different genotypes of rs2075674 and rs7385804. The mechanism remained to be explored in further studies.
Objective:To explore the gene-gene interaction of HFE and TFR2 on CHD.
Method:We used unconditional Logistic regression model and likehood test to evaluate the gene-gene interaction of HFE and TFR2.
Results:We found there were not interactions between the SNPs of HFE and TFR2, after adjustment for the conventional risk factors such as smoking, drinking, age, gender and family history of CHD, the results did not change, we did not find any significant associations between gene-gene interaction of HFE and TFR2 and CHD (P>0.05).
Conclusion:There were not significant associations between gene-gene interaction of HFE and TFR2 and CHD.
引文
[1]. You S A and Q Wang. Ferritin in atherosclerosis. Clinica chimica acta; international journal of clinical chemistry,2005,357(1):1-16.
[2]. Sullivan J L. Iron and the sex difference in heart disease risk Lancet,1981, 1(8233):1293-4.
[3]. Lapenna D, S D Pierdomenico, G Ciofani, et al. Association of body iron stores with low molecular weight iron and oxidant damage of human atherosclerotic plaques. Free Radic Biol Med,2007,42(4):492-8.
[4]. Araujo J A, E L Romano, B E Brito, et al. Iron overload augments the development of atherosclerotic lesions in rabbits. Arteriosclerosis, thrombosis, and vascular biology,1995,15(8):1172-80.
[5]. Lee T S, M S Shiao, C C Pan, et al. Iron-deficient diet reduces atherosclerotic lesions in apoE-deficient mice. Circulation,1999,99(9):1222-9.
[6]. Van Lenten B J, J Prieve, M Navab, et al. Lipid-induced changes in intracellular iron homeostasis in vitro and in vivo. The Journal of clinical investigation,1995, 95(5):2104-10.
[7]. van Jaarsveld H, G F Pool and H C Barnard. Influence of ferritin levels on LDL cholesterol concentration in women. Research communications in molecular pathology and pharmacology,1997,98(2):201-8.
[8]. Salonen J T, T P Tuomainen, R Salonen, et al. Donation of blood is associated with reduced risk of myocardial infarction. The Kuopio Ischaemic Heart Disease Risk Factor Study. American journal of epidemiology,1998,148(5):445-51.
[9]. Salonen J T, K Nyyssonen, H Korpela, et al. High stored iron levels are associated with excess risk of myocardial infarction in eastern Finnish men. Circulation,1992, 86(3):803-11.
[10]. Kiechl S, J Willeit, G Egger, et al. Body iron stores and the risk of carotid atherosclerosis:prospective results from the Bruneck study. Circulation,1997, 96(10):3300-7.
[11]. Manttari M, V Manninen, J K Huttunen, et al. Serum ferritin and ceruloplasmin as coronary risk factors. European heart journal,1994,15(12):1599-603.
[12]. Simon M, M Bourel, R Fauchet, et al. Association of HLA-A3 and HLA-B14 antigens with idiopathic haemochromatosis. Gut,1976,17(5):332-4.
[13]. Feder J N, A Gnirke, W Thomas, et al. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nature genetics,1996,13(4):399-408.
[14]. Darshan D, D M Frazer and G J Anderson. Molecular basis of iron-loading disorders. Expert reviews in molecular medicine,12:e36.
[15]. Tuomainen T P, K Kontula, K Nyyssonen, et al. Increased risk of acute myocardial infarction in carriers of the hemochromatosis gene Cys282Tyr mutation:a prospective cohort study in men in eastern Finland Circulation,1999, 100(12):1274-9.
[16]. Waalen J, V Felitti, T Gelbart, et al. Prevalence of coronary heart disease associated with HFE mutations in adults attending a health appraisal center. Am J Med,2002, 113(6):472-9.
[17]. Rhodes D A, R Raha-Chowdhury, T M Cox, et al. Homozygosity for the predominant Cys282Tyr mutation and absence of disease expression in hereditary haemochromatosis. J Med Genet,1997,34(9):761-4.
[18]. Roest M, Y T van der Schouw, B de Valk, et al. Heterozygosity for a hereditary hemochromatosis gene is associated with cardiovascular death in women. Circulation,1999,100(12):1268-73.
[19]. Rasmussen M L, A R Folsom, D J Catellier, et al. A prospective study of coronary heart disease and the hemochromatosis gene (HFE) C282Y mutation:the Atherosclerosis Risk in Communities (ARIC) study. Atherosclerosis,2001, 154(3):739-46.
[20]. Franco R F, M A Zago, M D Trip, et al. Prevalence of hereditary haemochromatosis in premature atherosclerotic vascular disease. British journal of haematology,1998, 102(5):1172-5.
[21]. Ellervik C, A Tybjaerg-Hansen, P Grande, et al. Hereditary hemochromatosis and risk of ischemic heart disease:a prospective study and a case-control study. Circulation,2005,112(2):185-93.
[22]. Moller D V, R Pecini, F Gustafsson, et al. Hereditary hemochromatosis (HFE) genotypes in heart failure:relation to etiology and prognosis. BMC medical genetics,11:117.
[23]. Battiloro E, D Ombres, E Pascale, et al. Haemochromatosis gene mutations and risk of coronary artery disease. Eur J Hum Genet,2000,8(5):389-92.
[24]. Nomenclature and criteria for diagnosis of ischemic heart disease. Report of the Joint International Society and Federation of Cardiology/World Health Organization task force on standardization of clinical nomenclature. Circulation,1979, 59(3):607-9.
[25]. Lee S H, J W Kim, S H Shin, et al. HFE gene mutations, serum ferritin level, transferrin saturation, and their clinical correlates in a Korean population. Digestive diseases and sciences,2009,54(4):879-86.
[26]. Ropero P, L Llorente, F A Gonzalez, et al. Incidence of the HFE gene mutations in a cohort of non-Spanish origin neonates in Madrid Annals of hematology,2007, 86(6):459-62.
[27]. Nie L, L Li, L Yang, et al. HFE genotype and iron metabolism in Chinese patients with myelodysplastic syndromes and aplastic anemia Annals of hematology, 89(12):1249-53.
[28]. 李剑红,朴建华,杨晓光.HFE基因突变在我国成年男性人群的分布.营养学报,2007,29(4)：324-7.
[29]. Stephens M and P Donnelly. A comparison of bayesian methods for haplotype reconstruction from population genotype data American journal of human genetics, 2003,73(5):1162-9.
[30]. McCance R A and E M Widdowson. The absorption and excretion of iron following oral and intravenous administration. The Journal of physiology,1938,94(1):148-54.
[31]. Cracowski J L, P Devillier, T Durand, et al. Vascular biology of the isoprostanes. J Vasc Res,2001,38(2):93-103.
[32]. 谢育萍,颜秀娟.氧化伤害之临床指标：Isoprostanes和Neuroprostanes.生物医学,2009,2(1)：53-67.
[33]. Duffy S J, E S Biegelsen, M Holbrook, et al. Iron chelation improves endothelial function in patients with coronary artery disease. Circulation,2001, 103(23):2799-804.
[34]. Nathanson M H and G D McLaren. Computer simulation of iron absorption: regulation of mucosal and systemic iron kinetics in dogs. The Journal of nutrition, 1987,117(6):1067-75.
[35]. Cavill I, M Worwood and A Jacobs. Internal regulation of iron absorption. Nature, 1975,256(5515):328-9.
[36]. Bauminger E R, P M Harrison, D Hechel, et al. Mossbauer spectroscopic investigation of structure-function relations in ferritins. Biochimica et biophysica acta,1991,1118(1):48-58.
[37]. Tuomainen T P, K Punnonen, K Nyyssonen, et al. Association between body iron stores and the risk of acute myocardial infarction in men. Circulation,1998, 97(15):1461-6.
[38]. Morrison H I, R M Semenciw, Y Mao, et al. Serum iron and risk of fatal acute myocardial infarction Epidemiology (Cambridge, Mass,1994,5(2):243-6.
[39]. Berge L N, K H Bonaa and A Nordoy. Serum ferritin, sex hormones, and cardiovascular risk factors in healthy women. Arterioscler Thromb,1994, 14(6):857-61.
[40]. Salonen J T, H Korpela, K Nyyssonen, et al. Lowering of body iron stores by blood letting and oxidation resistance of serum lipoproteins:a randomized cross-over trial in male smokers. Journal of internal medicine,1995,237(2):161-8.
[41]. Meyers D G,D Strickland, P A Maloley, et al. Possible association of a reduction in cardiovascular events with blood donation Heart (British Cardiac Society),1997, 78(2):188-93.
[42]. Meyers D G, K C Jensen and J E Menitove. A historical cohort study of the effect of lowering body iron through blood donation on incident cardiac events. Transfusion, 2002,42(9):1135-9.
[43]. Frey G H and D W Krider. Serum ferritin and myocardial infarct The West Virginia medical journal,1994,90(l):13-5.
[44]. Moore M, A R Folsom, R W Barnes, et al. No association between serum ferritin and asymptomatic carotid atherosclerosis. The Atherosclerosis Risk in Communities (ARIC) Study. American journal of epidemiology,1995,141(8):719-23.
[45]. van der A D, J J Marx, D E Grobbee, et al. Non-transferrin-bound iron and risk of coronary heart disease in postmenopausal women. Circulation,2006, 113(16):1942-9.
[46]. Sempos C T, A C Looker, R F Gillum, et al. Body iron stores and the risk of coronary heart disease. The New England journal of medicine,1994, 330(16):1119-24.
[47]. Ascherio A and W C Willett. Are body iron stores related to the risk of coronary heart disease? The New England journal of medicine,1994,330(16):1152-4.
[48]. Qi L, R M van Dam, K Rexrode, et al. Heme iron from diet as a risk factor for coronary heart disease in women with type 2 diabetes. Diabetes care,2007, 30(1):101-6.
[49]. Gabay C and I Kushner. Acute-phase proteins and other systemic responses to inflammation. The New England journal of medicine,1999,340(6):448-54.
[50]. van der A D, M M Rovers, D E Grobbee, et al. Mutations in the HFE gene and cardiovascular disease risk:an individual patient data meta-analysis of 53880 subjects. Circ Cardiovasc Genet,2008,1(1):43-50.
[51]. Claeys D, M Walting, F Julmy, et al. Haemochromatosis mutations and ferritin in myocardial infarction:a case-control study. European journal of clinical investigation,2002,32 Suppl 1:3-8.
[52]. Braun N A, R Covarrubias and A S Major. Natural killer T cells and atherosclerosis: form and function meet pathogenesis. J Innate Immun,2(4):316-24.
[53]. Giacconi R, C Caruso, D Lio, et al.1267 HSP70-2 polymorphism as a risk factor for carotid plaque rupture and cerebral ischaemia in old type 2 diabetes-atherosclerotic patients. Mech Ageing Dev,2005,126(8):866-73.
[54]. Badimon L, R F Storey and G Vilahur. Update on lipids, inflammation and atherothrombosis. Thrombosis and haemostasis, (Suppl.1).
[55]. Evangelopoulos A A, N G Vallianou, V Bountziouka, et al. Association between serum cystatin C, monocytes and other inflammatory markers. Internal medicine journal.
[56]. Maruna P, M Vokurka and J Lindner. Plasma hepcidin correlates positively with interleukin-6 in patients undergoing pulmonary endarterectomy. Physiological research/Academia Scientiarum Bohemoslovaca.
[57]. Valenti L, P Dongiovanni, B M Motta, et al. Serum hepcidin and macrophage iron correlate with MCP-1 release and vascular damage in patients with metabolic syndrome alterations. Arteriosclerosis, thrombosis, and vascular biology, 31(3):683-90.
[58]. West A P, Jr., M J Bennett, V M Sellers, et al. Comparison of the interactions of transferrin receptor and transferrin receptor 2 with transferrin and the hereditary hemochromatosis protein HFE. The Journal of biological chemistry,2000, 275(49):38135-8.
[59]. Camaschella C and A Roetto.1993.
[60]. Rovetta G, P Monteforte, L Buffrini, et al. Prevalence of HFE and TFR2 gene mutation in 118 Ligurian rheumatic patients. Minerva Med,2004,95(6):535-9.
[61]. Ma E S, K K Lam, A Y Chan, et al. Transferrin receptor-2 polymorphisms and iron overload in transfusion independent b-thalassemia intermedia Haematologica,2003, 88(3):345-6.
[62]. Lee P L, C Halloran, C West, et al. Mutation analysis of the transferrin receptor-2 gene in patients with iron overload Blood cells, molecules & diseases,2001, 27(1):285-9.
[63]. Barton E H, P A West, C A Rivers, et al. Transferrin receptor-2 (TFR2) mutation Y250X in Alabama Caucasian and African American subjects with and without primary iron overload. Blood cells, molecules & diseases,2001,27(1):279-84.
[64]. De Gobbi M, M R Barilaro, G Garozzo, et al. TFR2 Y250X mutation in Italy. Br J Haematol,2001,114(1):243-4.
[65]. Fleming R E, J R Ahmann, M C Migas, et al. Targeted mutagenesis of the murine transferrin receptor-2 gene produces hemochromatosis. Proc Natl Acad Sci U S A, 2002,99(16):10653-8.
[66]. He M A, X Zhang, J Wang, et al. Genetic variation in heat shock protein 60 gene and coronary heart disease in China:tagging-SNP haplotype analysis in a case-control study. Cell stress & chaperones,2008,13(2):231-8.
[67]. Zhou L, X Zhang, M He, et al. Associations between single nucleotide polymorphisms on chromosome 9p21 and risk of coronary heart disease in Chinese Han population. Arteriosclerosis, thrombosis, and vascular biology,2008, 28(11):2085-9.
[68]. Ross R. Atherosclerosis-an inflammatory disease. The New England journal of medicine,1999,340(2):115-26.
[69]. Hansson G K, P Libby, U Schonbeck, et al. Innate and adaptive immunity in the pathogenesis of atherosclerosis. Circulation research,2002,91(4):281-91.
[70]. Zhang X, M A He, L Cheng, et al. Joint effects of antibody to heat shock protein 60, hypertension, and diabetes on risk of coronary heart disease in Chinese. Clinical chemistry,2008,54(6):1046-52.
[71]. Stephens J W, S C Bain and S E Humphries. Gene-environment interaction and oxidative stress in cardiovascular disease. Atherosclerosis,2008,200(2):229-38.
[72]. He M A, L X Cheng, C Z Jiang, et al. Associations of polymorphism of P22(phox) C242T, plasma levels of vitamin E, and smoking with coronary heart disease in China American heart journal,2007,153(4):640 e1-6.
[1]. Bauminger E.R., Harrison P.M., Hechel D., et al. Mossbauer spectroscopic investigation of structure-function relations in ferritins. Biochimica et biophysica acta,1991,1118(1):48-58.
[2]. Harrison P.M. and Arosio P. The ferritins:molecular properties, iron storage function and cellular regulation. Biochimica et biophysica acta,1996,1275(3): 161-203.
[3]. McCance R.A. and Widdowson E.M. The absorption and excretion of iron following oral and intravenous administration. The Journal of physiology,1938, 94(1):148-154.
[4]. Anderson G.J., Frazer D.M. and McLaren G.D. Iron absorption and metabolism. Current opinion in gastroenterology,2009,25(2):129-135.
[5]. Nathanson M.H. and McLaren G.D. Computer simulation of iron absorption: regulation of mucosal and systemic iron kinetics in dogs. The Journal of nutrition, 1987,117(6):1067-1075.
[6]. Cavill I., Worwood M. and Jacobs A. Internal regulation of iron absorption Nature, 1975,256(5515):328-329.
[7]. Pietrangelo A. Hereditary hemochromatosis-a new look at an old disease. N Engl J Med,2004,350(23):2383-2397.
[8]. Leibold E.A. and Guo B. Iron-dependent regulation of ferritin and transferrin receptor expression by the iron-responsive element binding protein Annual review of nutrition,1992,12:345-368.
[9]. Wang J. and Pantopoulos K. Regulation of cellular iron metabolism. The Biochemical journal.434(3):365-381.
[10]. Sullivan J.L. Iron and the sex difference in heart disease risk Lancet,1981,1(8233): 1293-1294.
[11]. Yokomori N., Iwasa Y., Aida K., et al. Transcriptional regulation of ferritin messenger ribonucleic acid levels by insulin in cultured rat glioma cells. Endocrinology,1991,128(3):1474-1480.
[12]. Cazzola M., Bergamaschi G, Dezza L., et al. Manipulations of cellular iron metabolism for modulating normal and malignant cell proliferation:achievements and prospects. Blood,1990,75(10):1903-1919.
[13]. You S.A. and Wang Q. Ferritin in atherosclerosis. Clinica chimica acta; international journal of clinical chemistry,2005,357(1):1-16.
[14]. Ryan T.P. and Aust S.D. The role of iron in oxygen-mediated toxicities. Critical reviews in toxicology,1992,22(2):119-141.
[15]. Lapenna D., Pierdomenico S.D., Ciofani G, et al. Association of body iron stores with low molecular weight iron and oxidant damage of human atherosclerotic plaques. Free radical biology & medicine,2007,42(4):492-498.
[16]. Araujo J.A., Romano E.L., Brito B.E., et al. Iron overload augments the development of atherosclerotic lesions in rabbits. Arteriosclerosis, thrombosis, and vascular biology,1995,15(8):1172-1180.
[17]. Lee T.S., Shiao M.S., Pan C.C., et al. Iron-deficient diet reduces atherosclerotic lesions in apoE-deficient mice. Circulation,1999,99(9):1222-1229.
[18]. Van Lenten B.J., Prieve J., Navab M., et al. Lipid-induced changes in intracellular iron homeostasis in vitro and in vivo. The Journal of clinical investigation,1995, 95(5):2104-2110.
[19]. Berge L.N., Bonaa K.H. and Nordoy A. Plasma ferritin, sex hormones, and cardiovascular risk factors in healthy women. Arterioscler Thromb,1994,14(6): 857-861.
[20]. van Jaarsveld H., Pool G.F. and Barnard H.C. Influence of ferritin levels on LDL cholesterol concentration in women. Research communications in molecular pathology and pharmacology,1997,98(2):201-208.
[21]. Salonen J.T., Tuomainen T.P., Salonen R., et al. Donation of blood is associated with reduced risk of myocardial infarction. The Kuopio Ischaemic Heart Disease Risk Factor Study. American journal of epidemiology,1998,148(5):445-451.
[22]. Salonen J.T., Nyyssonen K., Korpela H., et al. High stored iron levels are associated with excess risk of myocardial infarction in eastern Finnish men. Circulation,1992, 86(3):803-811.
[23]. Kiechl S., Willeit J., Egger G, et al. Body iron stores and the risk of carotid atherosclerosis:prospective results from the Bruneck study. Circulation,1997, 96(10):3300-3307.
[24]. Tuomainen T.P., Punnonen K., Nyyssonen K., et al. Association between body iron stores and the risk of acute myocardial infarction in men. Circulation,1998,97(15): 1461-1466.
[25]. Morrison H.I., Semenciw R.M., Mao Y., et al. Plasma iron and risk of fatal acute myocardial infarction. Epidemiology (Cambridge, Mass,1994,5(2):243-246.
[26]. Manttari M., Manninen V., Huttunen J.K., et al. Plasma ferritin and ceruloplasmin as coronary risk factors. European heart journal,1994,15(12):1599-1603.
[27]. Frey G.H. and Krider D.W. Plasma ferritin and myocardial infarct The West Virginia medical journal,1994,90(1):13-15.
[28]. Moore M., Folsom A.R., Barnes R.W., et al. No association between plasma ferritin and asymptomatic carotid atherosclerosis. The Atherosclerosis Risk in Communities (ARIC) Study. American journal of epidemiology,1995,141(8):719-723.
[29]. Simon M., Bourel M., Fauchet R., et al. Association of HLA-A3 and HLA-B14 antigens with idiopathic haemochromatosis. Gut,1976,17(5):332-334.
[30]. Feder J.N., Gnirke A., Thomas W., et al. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nature genetics,1996,13(4): 399-408.
[31]. Parkkila S., Waheed A., Britton R.S., et al. Immunohistochemistry of HLA-H, the protein defective in patients with hereditary hemochromatosis, reveals unique pattern of expression in gastrointestinal tract Proceedings of the National Academy of Sciences of the United States of America,1997,94(6):2534-2539.
[32]. Bennett M.J., Lebron J:A. and Bjorkman P.J. Crystal structure of the hereditary haemochromatosis protein HFE complexed with transferrin receptor. Nature,2000, 403(6765):46-53.
[33]. Darshan D., Frazer D.M. and Anderson G.J. Molecular basis of iron-loading disorders. Expert Rev Mol Med.12:e36.
[34]. Powell L.W., Subramaniam V.N. and Yapp T.R. Haemochromatosis in the new millennium. Journal of hepatology,2000,32(1 Suppl):48-62.
[35]. Rochette J., Pointon J.J., Fisher C.A., et al. Multicentric origin of hemochromatosis gene (HFE) mutations. American journal of human genetics,1999,64(4): 1056-1062.
[36]. Gochee P.A., Powell L.W., Cullen D.J., et al. A population-based study of the biochemical and clinical expression of the H63D hemochromatosis mutation. Gastroenterology,2002,122(3):646-651.
[37]. Mura C., Raguenes O. and Ferec C. HFE mutations analysis in 711 hemochromatosis probands:evidence for S65C implication in mild form of hemochromatosis. Blood,1999,93(8):2502-2505.
[38]. Phatak P.D., Ryan D.H., Cappuccio J., et al. Prevalence and penetrance of HFE mutations in 4865 unselected primary care patients. Blood cells, molecules & diseases,2002,29(1):41-47.
[39]. Waalen J., Felitti V., Gelbart T., et al. Prevalence of coronary heart disease associated with HFE mutations in adults attending a health appraisal center. The American journal of medicine,2002,113(6):472-479.
[40]. Colli M.L., Gross J.L. and Canani L.H. Mutation H63D in the HFE gene confers risk for the development of type 2 diabetes mellitus but not for chronic complications. Journal of diabetes and its complications.25(1):25-30.
[41]. Ellervik C., Birgens H., Tybjaerg-Hansen A., et al. Hemochromatosis genotypes and risk of 31 disease endpoints:meta-analyses including 66,000 cases and 226,000 controls. Hepatology (Baltimore, Md,2007,46(4):1071-1080.
[42]. Sampietro M., Piperno A., Lupica L., et al. High prevalence of the His63Asp HFE mutation in Italian patients with porphyria cutanea tarda Hepatology (Baltimore, Md,1998,27(1):181-184.
[43]. Tuomainen T.P., Kontula K., Nyyssonen K., et al. Increased risk of acute myocardial infarction in carriers of the hemochromatosis gene Cys282Tyr mutation: a prospective cohort study in men in eastern Finland. Circulation,1999,100(12): 1274-1279.
[44]. Roest M., van der Schouw Y.T., de Valk B., et al. Heterozygosity for a hereditary hemochromatosis gene is associated with cardiovascular death in women. Circulation,1999,100(12):1268-1273.
[45]. Rasmussen M.L., Folsom A.R., Catellier D.J., et al. A prospective study of coronary heart disease and the hemochromatosis gene (HFE) C282Y mutation:the Atherosclerosis Risk in Communities (ARIC) study. Atherosclerosis,2001,154(3): 739-746.
[46]. Franco R.F., Zago M.A., Trip M.D., et al. Prevalence of hereditary haemochromatosis in premature atherosclerotic vascular disease. British journal of haematology,1998,102(5):1172-1175.
[47]. Ellervik C., Tybjaerg-Hansen A., Grande P., et al. Hereditary hemochromatosis and risk of ischemic heart disease:a prospective study and a case-control study. Circulation,2005,112(2):185-193.
[48]. Claeys D., Walting M., Julmy F., et al. Haemochromatosis mutations and ferritin in myocardial infarction:a case-control study. European journal of clinical investigation,2002,32 Suppl 1:3-8.
[49]. Moller D.V., Pecini R., Gustafsson F., et al. Hereditary hemochromatosis (HFE) genotypes in heart failure:relation to etiology and prognosis. BMC medical genetics.11:117.
[50]. Battiloro E., Ombres D., Pascale E., et al. Haemochromatosis gene mutations and risk of coronary artery disease. Eur J Hum Genet,2000,8(5):389-392.
[51]. Suominen P., Punnonen K., Rajamaki A., et al. Evaluation of new immunoenzymometric assay for measuring soluble transferrin receptor to detect iron deficiency in anemic patients. Clin Chem,1997,43(9):1641-1646.
[52]. 谢天培,吴孟超,沈锋,等.肝癌细胞膜上转铁蛋白受体和去唾液酸糖蛋白受体数量的变化.第二军医大学学报,1997,18(1)：6-8.
[53]. Kato J., Kohgo Y., Kondo H., et al. Circulating transferrin receptor in acute leukemias. Int J Hematol,1992,56(2):161-165.
[54]. Syrovatka P., Kraml P., Hulikova K., et al. Iron stores are associated with asymptomatic atherosclerosis in healthy men of primary prevention. Eur J Clin Invest.
[55]. Nanami M., Ookawara T., Otaki Y, et al. Tumor necrosis factor-alpha-induced iron sequestration and oxidative stress in human endothelial cells. Arterioscler Thromb Vasc Biol,2005,25(12):2495-2501.
[56]. Katz M.F., Farber H.W., Dodds-Stitt Z., et al. Serotonin-stimulated aortic endothelial cells secrete a novel T lymphocyte chemotactic and growth factor. J Leukoc Biol,1994,55(5):567-573.
[57]. Zhao N., Sun Z., Mao Y, et al. Myocardial iron metabolism in the regulation of cardiovascular diseases in rats. Cell Physiol Biochem.25(6):587-594.
[58]. West A.P., Jr., Bennett M.J., Sellers V.M., et al. Comparison of the interactions of transferrin receptor and transferrin receptor 2 with transferrin and the hereditary hemochromatosis protein HFE. J Biol Chem,2000,275(49):38135-38138.
[59]. Fleming R.E., Ahmann J.R., Migas M.C., et al. Targeted mutagenesis of the murine transferrin receptor-2 gene produces hemochromatosis. Proc Natl Acad Sci U S A, 2002,99(16):10653-10658.
[60]. Camaschella C. and Roetto A.TFR2-Related Hereditary Hemochromatosis.1993.
[61]. Girelli D., Bozzini C., Roetto A., et al. Clinical and pathologic findings in hemochromatosis type 3 due to a novel mutation in transferrin receptor 2 gene. Gastroenterology,2002,122(5):1295-1302.
[62]. Roetto A., Totaro A., Piperno A., et al. New mutations inactivating transferrin receptor 2 in hemochromatosis type 3. Blood,2001,97(9):2555-2560.
[63]. Rovetta G, Monteforte P., Buffrini L., et al. Prevalence of HFE and TFR2 gene mutation in 118 Ligurian rheumatic patients. Minerva Med,2004,95(6):535-539.
[64]. Ma E.S., Lam K.K., Chan A.Y., et al. Transferrin receptor-2 polymorphisms and iron overload in transfusion independent b-thalassemia intermedia Haematologica, 2003,88(3):345-346.
[65]. Lee P.L., Halloran C., West C., et al. Mutation analysis of the transferrin receptor-2 gene in patients with iron overload. Blood cells, molecules & diseases,2001,27(1): 285-289.
[66]. Fleming R.E. and Sly W.S. Hepcidin:a putative iron-regulatory hormone relevant to hereditary hemochromatosis and the anemia of chronic disease. Proceedings of the National Academy of Sciences of the United States of America,2001,98(15): 8160-8162.
[67]. Nicolas G, Bennoun M., Devaux I., et al. Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice. Proceedings of the National Academy of Sciences of the United States of America, 2001,98(15):8780-8785.
[68]. Krause A., Neitz S., Magert H.J., et al. LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity. FEBS letters,2000,480(2-3): 147-150.
[69]. Park C.H., Valore E.V., Waring A.J., et al. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. The Journal of biological chemistry,2001,276(11): 7806-7810.
[70]. Nicolas G, Viatte L., Bennoun M., et al. Hepcidin, a new iron regulatory peptide. Blood cells, molecules & diseases,2002,29(3):327-335.
[71]. Nemeth E., Tuttle M.S., Powelson J., et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science (New York, N.Y, 2004,306(5704):2090-2093.
[72]. Santos M., Clevers H., de Sousa M., et al. Adaptive response of iron absorption to anemia, increased erythropoiesis, iron deficiency, and iron loading in beta2-microglobulin knockout mice. Blood,1998,91(8):3059-3065.
[73]. Pigeon C., Ilyin G, Courselaud B., et al. A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. The Journal of biological chemistry,2001,276(11): 7811-7819.
[74]. Wang Q., Du F., Qian Z.M., et al. Lipopolysaccharide induces a significant increase in expression of iron regulatory hormone hepcidin in the cortex and substantia nigra in rat brain. Endocrinology,2008,149(8):3920-3925.
[75]. Lee P., Peng H., Gelbart T., et al. Regulation of hepcidin transcription by interleukin-1 and interleukin-6. Proceedings of the National Academy of Sciences of the United States of America,2005,102(6):1906-1910.
[76]. Nemeth E., Rivera S., Gabayan V., et al. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. The Journal of clinical investigation,2004,113(9):1271-1276.
[77]. Pak M., Lopez M.A., Gabayan V., et al. Suppression of hepcidin during anemia requires erythropoietic activity. Blood,2006,108(12):3730-3735.
[78]. Origa R., Galanello R., Ganz T., et al. Liver iron concentrations and urinary hepcidin in beta-thalassemia Haematologica,2007,92(5):583-588.
[79]. Huang F.W., Pinkus J.L., Pinkus G.S., et al. A mouse model of juvenile hemochromatosis. The Journal of clinical investigation,2005,115(8):2187-2191.
[80]. Santos P.C., Cancado R.D., Pereira A.C., et al. Hereditary hemochromatosis: Mutations in genes involved in iron homeostasis in Brazilian patients. Blood cells, molecules & diseases.46(4):302-307.
[81]. Merle U., Fein E., Gehrke S.G., et al. The iron regulatory peptide hepcidin is expressed in the heart and regulated by hypoxia and inflammation. Endocrinology, 2007,148(6):2663-2668.
[82]. Simonis G, Mueller K., Schwarz P., et al. The iron-regulatory peptide hepcidin is upregulated in the ischemic and in the remote myocardium after myocardial infarction. Peptides.31(9):1786-1790.
[83]. Maruna P., Vokurka M. and Lindner J. Plasma hepcidin correlates positively with interleukin-6 in patients undergoing pulmonary endarterectomy. Physiological research/Academia Scientiarum Bohemoslovaca.
[84]. Valenti L., Dongiovanni P., Motta B.M., et al. Plasma hepcidin and macrophage iron correlate with MCP-1 release and vascular damage in patients with metabolic syndrome alterations. Arteriosclerosis, thrombosis, and vascular biology.31(3): 683-690.
[85]. Badimon L., Storey R.F. and Vilahur G. Update on lipids, inflammation and atherothrombosis. Thrombosis and haemostasis, (Suppl.1).
[86]. Evangelopoulos A.A., Vallianou N.G., Bountziouka V., et al. Association between plasma cystatin C, monocytes and other inflammatory markers. Internal medicine journal.
[2]. Sullivan J L. Iron and the sex difference in heart disease risk Lancet,1981, 1(8233):1293-4.
[3]. Lapenna D, S D Pierdomenico, G Ciofani, et al. Association of body iron stores with low molecular weight iron and oxidant damage of human atherosclerotic plaques. Free Radic Biol Med,2007,42(4):492-8.
[4]. Araujo J A, E L Romano, B E Brito, et al. Iron overload augments the development of atherosclerotic lesions in rabbits. Arteriosclerosis, thrombosis, and vascular biology,1995,15(8):1172-80.
[5]. Lee T S, M S Shiao, C C Pan, et al. Iron-deficient diet reduces atherosclerotic lesions in apoE-deficient mice. Circulation,1999,99(9):1222-9.
[6]. Van Lenten B J, J Prieve, M Navab, et al. Lipid-induced changes in intracellular iron homeostasis in vitro and in vivo. The Journal of clinical investigation,1995, 95(5):2104-10.
[7]. van Jaarsveld H, G F Pool and H C Barnard. Influence of ferritin levels on LDL cholesterol concentration in women. Research communications in molecular pathology and pharmacology,1997,98(2):201-8.
[8]. Salonen J T, T P Tuomainen, R Salonen, et al. Donation of blood is associated with reduced risk of myocardial infarction. The Kuopio Ischaemic Heart Disease Risk Factor Study. American journal of epidemiology,1998,148(5):445-51.
[9]. Salonen J T, K Nyyssonen, H Korpela, et al. High stored iron levels are associated with excess risk of myocardial infarction in eastern Finnish men. Circulation,1992, 86(3):803-11.
[10]. Kiechl S, J Willeit, G Egger, et al. Body iron stores and the risk of carotid atherosclerosis:prospective results from the Bruneck study. Circulation,1997, 96(10):3300-7.
[11]. Manttari M, V Manninen, J K Huttunen, et al. Serum ferritin and ceruloplasmin as coronary risk factors. European heart journal,1994,15(12):1599-603.
[12]. Simon M, M Bourel, R Fauchet, et al. Association of HLA-A3 and HLA-B14 antigens with idiopathic haemochromatosis. Gut,1976,17(5):332-4.
[13]. Feder J N, A Gnirke, W Thomas, et al. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nature genetics,1996,13(4):399-408.
[14]. Darshan D, D M Frazer and G J Anderson. Molecular basis of iron-loading disorders. Expert reviews in molecular medicine,12:e36.
[15]. Tuomainen T P, K Kontula, K Nyyssonen, et al. Increased risk of acute myocardial infarction in carriers of the hemochromatosis gene Cys282Tyr mutation:a prospective cohort study in men in eastern Finland Circulation,1999, 100(12):1274-9.
[16]. Waalen J, V Felitti, T Gelbart, et al. Prevalence of coronary heart disease associated with HFE mutations in adults attending a health appraisal center. Am J Med,2002, 113(6):472-9.
[17]. Rhodes D A, R Raha-Chowdhury, T M Cox, et al. Homozygosity for the predominant Cys282Tyr mutation and absence of disease expression in hereditary haemochromatosis. J Med Genet,1997,34(9):761-4.
[18]. Roest M, Y T van der Schouw, B de Valk, et al. Heterozygosity for a hereditary hemochromatosis gene is associated with cardiovascular death in women. Circulation,1999,100(12):1268-73.
[19]. Rasmussen M L, A R Folsom, D J Catellier, et al. A prospective study of coronary heart disease and the hemochromatosis gene (HFE) C282Y mutation:the Atherosclerosis Risk in Communities (ARIC) study. Atherosclerosis,2001, 154(3):739-46.
[20]. Franco R F, M A Zago, M D Trip, et al. Prevalence of hereditary haemochromatosis in premature atherosclerotic vascular disease. British journal of haematology,1998, 102(5):1172-5.
[21]. Ellervik C, A Tybjaerg-Hansen, P Grande, et al. Hereditary hemochromatosis and risk of ischemic heart disease:a prospective study and a case-control study. Circulation,2005,112(2):185-93.
[22]. Moller D V, R Pecini, F Gustafsson, et al. Hereditary hemochromatosis (HFE) genotypes in heart failure:relation to etiology and prognosis. BMC medical genetics,11:117.
[23]. Battiloro E, D Ombres, E Pascale, et al. Haemochromatosis gene mutations and risk of coronary artery disease. Eur J Hum Genet,2000,8(5):389-92.
[24]. Nomenclature and criteria for diagnosis of ischemic heart disease. Report of the Joint International Society and Federation of Cardiology/World Health Organization task force on standardization of clinical nomenclature. Circulation,1979, 59(3):607-9.
[25]. Lee S H, J W Kim, S H Shin, et al. HFE gene mutations, serum ferritin level, transferrin saturation, and their clinical correlates in a Korean population. Digestive diseases and sciences,2009,54(4):879-86.
[26]. Ropero P, L Llorente, F A Gonzalez, et al. Incidence of the HFE gene mutations in a cohort of non-Spanish origin neonates in Madrid Annals of hematology,2007, 86(6):459-62.
[27]. Nie L, L Li, L Yang, et al. HFE genotype and iron metabolism in Chinese patients with myelodysplastic syndromes and aplastic anemia Annals of hematology, 89(12):1249-53.
[28]. 李剑红,朴建华,杨晓光.HFE基因突变在我国成年男性人群的分布.营养学报,2007,29(4)：324-7.
[29]. Stephens M and P Donnelly. A comparison of bayesian methods for haplotype reconstruction from population genotype data American journal of human genetics, 2003,73(5):1162-9.
[30]. McCance R A and E M Widdowson. The absorption and excretion of iron following oral and intravenous administration. The Journal of physiology,1938,94(1):148-54.
[31]. Cracowski J L, P Devillier, T Durand, et al. Vascular biology of the isoprostanes. J Vasc Res,2001,38(2):93-103.
[32]. 谢育萍,颜秀娟.氧化伤害之临床指标：Isoprostanes和Neuroprostanes.生物医学,2009,2(1)：53-67.
[33]. Duffy S J, E S Biegelsen, M Holbrook, et al. Iron chelation improves endothelial function in patients with coronary artery disease. Circulation,2001, 103(23):2799-804.
[34]. Nathanson M H and G D McLaren. Computer simulation of iron absorption: regulation of mucosal and systemic iron kinetics in dogs. The Journal of nutrition, 1987,117(6):1067-75.
[35]. Cavill I, M Worwood and A Jacobs. Internal regulation of iron absorption. Nature, 1975,256(5515):328-9.
[36]. Bauminger E R, P M Harrison, D Hechel, et al. Mossbauer spectroscopic investigation of structure-function relations in ferritins. Biochimica et biophysica acta,1991,1118(1):48-58.
[37]. Tuomainen T P, K Punnonen, K Nyyssonen, et al. Association between body iron stores and the risk of acute myocardial infarction in men. Circulation,1998, 97(15):1461-6.
[38]. Morrison H I, R M Semenciw, Y Mao, et al. Serum iron and risk of fatal acute myocardial infarction Epidemiology (Cambridge, Mass,1994,5(2):243-6.
[39]. Berge L N, K H Bonaa and A Nordoy. Serum ferritin, sex hormones, and cardiovascular risk factors in healthy women. Arterioscler Thromb,1994, 14(6):857-61.
[40]. Salonen J T, H Korpela, K Nyyssonen, et al. Lowering of body iron stores by blood letting and oxidation resistance of serum lipoproteins:a randomized cross-over trial in male smokers. Journal of internal medicine,1995,237(2):161-8.
[41]. Meyers D G,D Strickland, P A Maloley, et al. Possible association of a reduction in cardiovascular events with blood donation Heart (British Cardiac Society),1997, 78(2):188-93.
[42]. Meyers D G, K C Jensen and J E Menitove. A historical cohort study of the effect of lowering body iron through blood donation on incident cardiac events. Transfusion, 2002,42(9):1135-9.
[43]. Frey G H and D W Krider. Serum ferritin and myocardial infarct The West Virginia medical journal,1994,90(l):13-5.
[44]. Moore M, A R Folsom, R W Barnes, et al. No association between serum ferritin and asymptomatic carotid atherosclerosis. The Atherosclerosis Risk in Communities (ARIC) Study. American journal of epidemiology,1995,141(8):719-23.
[45]. van der A D, J J Marx, D E Grobbee, et al. Non-transferrin-bound iron and risk of coronary heart disease in postmenopausal women. Circulation,2006, 113(16):1942-9.
[46]. Sempos C T, A C Looker, R F Gillum, et al. Body iron stores and the risk of coronary heart disease. The New England journal of medicine,1994, 330(16):1119-24.
[47]. Ascherio A and W C Willett. Are body iron stores related to the risk of coronary heart disease? The New England journal of medicine,1994,330(16):1152-4.
[48]. Qi L, R M van Dam, K Rexrode, et al. Heme iron from diet as a risk factor for coronary heart disease in women with type 2 diabetes. Diabetes care,2007, 30(1):101-6.
[49]. Gabay C and I Kushner. Acute-phase proteins and other systemic responses to inflammation. The New England journal of medicine,1999,340(6):448-54.
[50]. van der A D, M M Rovers, D E Grobbee, et al. Mutations in the HFE gene and cardiovascular disease risk:an individual patient data meta-analysis of 53880 subjects. Circ Cardiovasc Genet,2008,1(1):43-50.
[51]. Claeys D, M Walting, F Julmy, et al. Haemochromatosis mutations and ferritin in myocardial infarction:a case-control study. European journal of clinical investigation,2002,32 Suppl 1:3-8.
[52]. Braun N A, R Covarrubias and A S Major. Natural killer T cells and atherosclerosis: form and function meet pathogenesis. J Innate Immun,2(4):316-24.
[53]. Giacconi R, C Caruso, D Lio, et al.1267 HSP70-2 polymorphism as a risk factor for carotid plaque rupture and cerebral ischaemia in old type 2 diabetes-atherosclerotic patients. Mech Ageing Dev,2005,126(8):866-73.
[54]. Badimon L, R F Storey and G Vilahur. Update on lipids, inflammation and atherothrombosis. Thrombosis and haemostasis, (Suppl.1).
[55]. Evangelopoulos A A, N G Vallianou, V Bountziouka, et al. Association between serum cystatin C, monocytes and other inflammatory markers. Internal medicine journal.
[56]. Maruna P, M Vokurka and J Lindner. Plasma hepcidin correlates positively with interleukin-6 in patients undergoing pulmonary endarterectomy. Physiological research/Academia Scientiarum Bohemoslovaca.
[57]. Valenti L, P Dongiovanni, B M Motta, et al. Serum hepcidin and macrophage iron correlate with MCP-1 release and vascular damage in patients with metabolic syndrome alterations. Arteriosclerosis, thrombosis, and vascular biology, 31(3):683-90.
[58]. West A P, Jr., M J Bennett, V M Sellers, et al. Comparison of the interactions of transferrin receptor and transferrin receptor 2 with transferrin and the hereditary hemochromatosis protein HFE. The Journal of biological chemistry,2000, 275(49):38135-8.
[59]. Camaschella C and A Roetto.1993.
[60]. Rovetta G, P Monteforte, L Buffrini, et al. Prevalence of HFE and TFR2 gene mutation in 118 Ligurian rheumatic patients. Minerva Med,2004,95(6):535-9.
[61]. Ma E S, K K Lam, A Y Chan, et al. Transferrin receptor-2 polymorphisms and iron overload in transfusion independent b-thalassemia intermedia Haematologica,2003, 88(3):345-6.
[62]. Lee P L, C Halloran, C West, et al. Mutation analysis of the transferrin receptor-2 gene in patients with iron overload Blood cells, molecules & diseases,2001, 27(1):285-9.
[63]. Barton E H, P A West, C A Rivers, et al. Transferrin receptor-2 (TFR2) mutation Y250X in Alabama Caucasian and African American subjects with and without primary iron overload. Blood cells, molecules & diseases,2001,27(1):279-84.
[64]. De Gobbi M, M R Barilaro, G Garozzo, et al. TFR2 Y250X mutation in Italy. Br J Haematol,2001,114(1):243-4.
[65]. Fleming R E, J R Ahmann, M C Migas, et al. Targeted mutagenesis of the murine transferrin receptor-2 gene produces hemochromatosis. Proc Natl Acad Sci U S A, 2002,99(16):10653-8.
[66]. He M A, X Zhang, J Wang, et al. Genetic variation in heat shock protein 60 gene and coronary heart disease in China:tagging-SNP haplotype analysis in a case-control study. Cell stress & chaperones,2008,13(2):231-8.
[67]. Zhou L, X Zhang, M He, et al. Associations between single nucleotide polymorphisms on chromosome 9p21 and risk of coronary heart disease in Chinese Han population. Arteriosclerosis, thrombosis, and vascular biology,2008, 28(11):2085-9.
[68]. Ross R. Atherosclerosis-an inflammatory disease. The New England journal of medicine,1999,340(2):115-26.
[69]. Hansson G K, P Libby, U Schonbeck, et al. Innate and adaptive immunity in the pathogenesis of atherosclerosis. Circulation research,2002,91(4):281-91.
[70]. Zhang X, M A He, L Cheng, et al. Joint effects of antibody to heat shock protein 60, hypertension, and diabetes on risk of coronary heart disease in Chinese. Clinical chemistry,2008,54(6):1046-52.
[71]. Stephens J W, S C Bain and S E Humphries. Gene-environment interaction and oxidative stress in cardiovascular disease. Atherosclerosis,2008,200(2):229-38.
[72]. He M A, L X Cheng, C Z Jiang, et al. Associations of polymorphism of P22(phox) C242T, plasma levels of vitamin E, and smoking with coronary heart disease in China American heart journal,2007,153(4):640 e1-6.
[1]. Bauminger E.R., Harrison P.M., Hechel D., et al. Mossbauer spectroscopic investigation of structure-function relations in ferritins. Biochimica et biophysica acta,1991,1118(1):48-58.
[2]. Harrison P.M. and Arosio P. The ferritins:molecular properties, iron storage function and cellular regulation. Biochimica et biophysica acta,1996,1275(3): 161-203.
[3]. McCance R.A. and Widdowson E.M. The absorption and excretion of iron following oral and intravenous administration. The Journal of physiology,1938, 94(1):148-154.
[4]. Anderson G.J., Frazer D.M. and McLaren G.D. Iron absorption and metabolism. Current opinion in gastroenterology,2009,25(2):129-135.
[5]. Nathanson M.H. and McLaren G.D. Computer simulation of iron absorption: regulation of mucosal and systemic iron kinetics in dogs. The Journal of nutrition, 1987,117(6):1067-1075.
[6]. Cavill I., Worwood M. and Jacobs A. Internal regulation of iron absorption Nature, 1975,256(5515):328-329.
[7]. Pietrangelo A. Hereditary hemochromatosis-a new look at an old disease. N Engl J Med,2004,350(23):2383-2397.
[8]. Leibold E.A. and Guo B. Iron-dependent regulation of ferritin and transferrin receptor expression by the iron-responsive element binding protein Annual review of nutrition,1992,12:345-368.
[9]. Wang J. and Pantopoulos K. Regulation of cellular iron metabolism. The Biochemical journal.434(3):365-381.
[10]. Sullivan J.L. Iron and the sex difference in heart disease risk Lancet,1981,1(8233): 1293-1294.
[11]. Yokomori N., Iwasa Y., Aida K., et al. Transcriptional regulation of ferritin messenger ribonucleic acid levels by insulin in cultured rat glioma cells. Endocrinology,1991,128(3):1474-1480.
[12]. Cazzola M., Bergamaschi G, Dezza L., et al. Manipulations of cellular iron metabolism for modulating normal and malignant cell proliferation:achievements and prospects. Blood,1990,75(10):1903-1919.
[13]. You S.A. and Wang Q. Ferritin in atherosclerosis. Clinica chimica acta; international journal of clinical chemistry,2005,357(1):1-16.
[14]. Ryan T.P. and Aust S.D. The role of iron in oxygen-mediated toxicities. Critical reviews in toxicology,1992,22(2):119-141.
[15]. Lapenna D., Pierdomenico S.D., Ciofani G, et al. Association of body iron stores with low molecular weight iron and oxidant damage of human atherosclerotic plaques. Free radical biology & medicine,2007,42(4):492-498.
[16]. Araujo J.A., Romano E.L., Brito B.E., et al. Iron overload augments the development of atherosclerotic lesions in rabbits. Arteriosclerosis, thrombosis, and vascular biology,1995,15(8):1172-1180.
[17]. Lee T.S., Shiao M.S., Pan C.C., et al. Iron-deficient diet reduces atherosclerotic lesions in apoE-deficient mice. Circulation,1999,99(9):1222-1229.
[18]. Van Lenten B.J., Prieve J., Navab M., et al. Lipid-induced changes in intracellular iron homeostasis in vitro and in vivo. The Journal of clinical investigation,1995, 95(5):2104-2110.
[19]. Berge L.N., Bonaa K.H. and Nordoy A. Plasma ferritin, sex hormones, and cardiovascular risk factors in healthy women. Arterioscler Thromb,1994,14(6): 857-861.
[20]. van Jaarsveld H., Pool G.F. and Barnard H.C. Influence of ferritin levels on LDL cholesterol concentration in women. Research communications in molecular pathology and pharmacology,1997,98(2):201-208.
[21]. Salonen J.T., Tuomainen T.P., Salonen R., et al. Donation of blood is associated with reduced risk of myocardial infarction. The Kuopio Ischaemic Heart Disease Risk Factor Study. American journal of epidemiology,1998,148(5):445-451.
[22]. Salonen J.T., Nyyssonen K., Korpela H., et al. High stored iron levels are associated with excess risk of myocardial infarction in eastern Finnish men. Circulation,1992, 86(3):803-811.
[23]. Kiechl S., Willeit J., Egger G, et al. Body iron stores and the risk of carotid atherosclerosis:prospective results from the Bruneck study. Circulation,1997, 96(10):3300-3307.
[24]. Tuomainen T.P., Punnonen K., Nyyssonen K., et al. Association between body iron stores and the risk of acute myocardial infarction in men. Circulation,1998,97(15): 1461-1466.
[25]. Morrison H.I., Semenciw R.M., Mao Y., et al. Plasma iron and risk of fatal acute myocardial infarction. Epidemiology (Cambridge, Mass,1994,5(2):243-246.
[26]. Manttari M., Manninen V., Huttunen J.K., et al. Plasma ferritin and ceruloplasmin as coronary risk factors. European heart journal,1994,15(12):1599-1603.
[27]. Frey G.H. and Krider D.W. Plasma ferritin and myocardial infarct The West Virginia medical journal,1994,90(1):13-15.
[28]. Moore M., Folsom A.R., Barnes R.W., et al. No association between plasma ferritin and asymptomatic carotid atherosclerosis. The Atherosclerosis Risk in Communities (ARIC) Study. American journal of epidemiology,1995,141(8):719-723.
[29]. Simon M., Bourel M., Fauchet R., et al. Association of HLA-A3 and HLA-B14 antigens with idiopathic haemochromatosis. Gut,1976,17(5):332-334.
[30]. Feder J.N., Gnirke A., Thomas W., et al. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nature genetics,1996,13(4): 399-408.
[31]. Parkkila S., Waheed A., Britton R.S., et al. Immunohistochemistry of HLA-H, the protein defective in patients with hereditary hemochromatosis, reveals unique pattern of expression in gastrointestinal tract Proceedings of the National Academy of Sciences of the United States of America,1997,94(6):2534-2539.
[32]. Bennett M.J., Lebron J:A. and Bjorkman P.J. Crystal structure of the hereditary haemochromatosis protein HFE complexed with transferrin receptor. Nature,2000, 403(6765):46-53.
[33]. Darshan D., Frazer D.M. and Anderson G.J. Molecular basis of iron-loading disorders. Expert Rev Mol Med.12:e36.
[34]. Powell L.W., Subramaniam V.N. and Yapp T.R. Haemochromatosis in the new millennium. Journal of hepatology,2000,32(1 Suppl):48-62.
[35]. Rochette J., Pointon J.J., Fisher C.A., et al. Multicentric origin of hemochromatosis gene (HFE) mutations. American journal of human genetics,1999,64(4): 1056-1062.
[36]. Gochee P.A., Powell L.W., Cullen D.J., et al. A population-based study of the biochemical and clinical expression of the H63D hemochromatosis mutation. Gastroenterology,2002,122(3):646-651.
[37]. Mura C., Raguenes O. and Ferec C. HFE mutations analysis in 711 hemochromatosis probands:evidence for S65C implication in mild form of hemochromatosis. Blood,1999,93(8):2502-2505.
[38]. Phatak P.D., Ryan D.H., Cappuccio J., et al. Prevalence and penetrance of HFE mutations in 4865 unselected primary care patients. Blood cells, molecules & diseases,2002,29(1):41-47.
[39]. Waalen J., Felitti V., Gelbart T., et al. Prevalence of coronary heart disease associated with HFE mutations in adults attending a health appraisal center. The American journal of medicine,2002,113(6):472-479.
[40]. Colli M.L., Gross J.L. and Canani L.H. Mutation H63D in the HFE gene confers risk for the development of type 2 diabetes mellitus but not for chronic complications. Journal of diabetes and its complications.25(1):25-30.
[41]. Ellervik C., Birgens H., Tybjaerg-Hansen A., et al. Hemochromatosis genotypes and risk of 31 disease endpoints:meta-analyses including 66,000 cases and 226,000 controls. Hepatology (Baltimore, Md,2007,46(4):1071-1080.
[42]. Sampietro M., Piperno A., Lupica L., et al. High prevalence of the His63Asp HFE mutation in Italian patients with porphyria cutanea tarda Hepatology (Baltimore, Md,1998,27(1):181-184.
[43]. Tuomainen T.P., Kontula K., Nyyssonen K., et al. Increased risk of acute myocardial infarction in carriers of the hemochromatosis gene Cys282Tyr mutation: a prospective cohort study in men in eastern Finland. Circulation,1999,100(12): 1274-1279.
[44]. Roest M., van der Schouw Y.T., de Valk B., et al. Heterozygosity for a hereditary hemochromatosis gene is associated with cardiovascular death in women. Circulation,1999,100(12):1268-1273.
[45]. Rasmussen M.L., Folsom A.R., Catellier D.J., et al. A prospective study of coronary heart disease and the hemochromatosis gene (HFE) C282Y mutation:the Atherosclerosis Risk in Communities (ARIC) study. Atherosclerosis,2001,154(3): 739-746.
[46]. Franco R.F., Zago M.A., Trip M.D., et al. Prevalence of hereditary haemochromatosis in premature atherosclerotic vascular disease. British journal of haematology,1998,102(5):1172-1175.
[47]. Ellervik C., Tybjaerg-Hansen A., Grande P., et al. Hereditary hemochromatosis and risk of ischemic heart disease:a prospective study and a case-control study. Circulation,2005,112(2):185-193.
[48]. Claeys D., Walting M., Julmy F., et al. Haemochromatosis mutations and ferritin in myocardial infarction:a case-control study. European journal of clinical investigation,2002,32 Suppl 1:3-8.
[49]. Moller D.V., Pecini R., Gustafsson F., et al. Hereditary hemochromatosis (HFE) genotypes in heart failure:relation to etiology and prognosis. BMC medical genetics.11:117.
[50]. Battiloro E., Ombres D., Pascale E., et al. Haemochromatosis gene mutations and risk of coronary artery disease. Eur J Hum Genet,2000,8(5):389-392.
[51]. Suominen P., Punnonen K., Rajamaki A., et al. Evaluation of new immunoenzymometric assay for measuring soluble transferrin receptor to detect iron deficiency in anemic patients. Clin Chem,1997,43(9):1641-1646.
[52]. 谢天培,吴孟超,沈锋,等.肝癌细胞膜上转铁蛋白受体和去唾液酸糖蛋白受体数量的变化.第二军医大学学报,1997,18(1)：6-8.
[53]. Kato J., Kohgo Y., Kondo H., et al. Circulating transferrin receptor in acute leukemias. Int J Hematol,1992,56(2):161-165.
[54]. Syrovatka P., Kraml P., Hulikova K., et al. Iron stores are associated with asymptomatic atherosclerosis in healthy men of primary prevention. Eur J Clin Invest.
[55]. Nanami M., Ookawara T., Otaki Y, et al. Tumor necrosis factor-alpha-induced iron sequestration and oxidative stress in human endothelial cells. Arterioscler Thromb Vasc Biol,2005,25(12):2495-2501.
[56]. Katz M.F., Farber H.W., Dodds-Stitt Z., et al. Serotonin-stimulated aortic endothelial cells secrete a novel T lymphocyte chemotactic and growth factor. J Leukoc Biol,1994,55(5):567-573.
[57]. Zhao N., Sun Z., Mao Y, et al. Myocardial iron metabolism in the regulation of cardiovascular diseases in rats. Cell Physiol Biochem.25(6):587-594.
[58]. West A.P., Jr., Bennett M.J., Sellers V.M., et al. Comparison of the interactions of transferrin receptor and transferrin receptor 2 with transferrin and the hereditary hemochromatosis protein HFE. J Biol Chem,2000,275(49):38135-38138.
[59]. Fleming R.E., Ahmann J.R., Migas M.C., et al. Targeted mutagenesis of the murine transferrin receptor-2 gene produces hemochromatosis. Proc Natl Acad Sci U S A, 2002,99(16):10653-10658.
[60]. Camaschella C. and Roetto A.TFR2-Related Hereditary Hemochromatosis.1993.
[61]. Girelli D., Bozzini C., Roetto A., et al. Clinical and pathologic findings in hemochromatosis type 3 due to a novel mutation in transferrin receptor 2 gene. Gastroenterology,2002,122(5):1295-1302.
[62]. Roetto A., Totaro A., Piperno A., et al. New mutations inactivating transferrin receptor 2 in hemochromatosis type 3. Blood,2001,97(9):2555-2560.
[63]. Rovetta G, Monteforte P., Buffrini L., et al. Prevalence of HFE and TFR2 gene mutation in 118 Ligurian rheumatic patients. Minerva Med,2004,95(6):535-539.
[64]. Ma E.S., Lam K.K., Chan A.Y., et al. Transferrin receptor-2 polymorphisms and iron overload in transfusion independent b-thalassemia intermedia Haematologica, 2003,88(3):345-346.
[65]. Lee P.L., Halloran C., West C., et al. Mutation analysis of the transferrin receptor-2 gene in patients with iron overload. Blood cells, molecules & diseases,2001,27(1): 285-289.
[66]. Fleming R.E. and Sly W.S. Hepcidin:a putative iron-regulatory hormone relevant to hereditary hemochromatosis and the anemia of chronic disease. Proceedings of the National Academy of Sciences of the United States of America,2001,98(15): 8160-8162.
[67]. Nicolas G, Bennoun M., Devaux I., et al. Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice. Proceedings of the National Academy of Sciences of the United States of America, 2001,98(15):8780-8785.
[68]. Krause A., Neitz S., Magert H.J., et al. LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity. FEBS letters,2000,480(2-3): 147-150.
[69]. Park C.H., Valore E.V., Waring A.J., et al. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. The Journal of biological chemistry,2001,276(11): 7806-7810.
[70]. Nicolas G, Viatte L., Bennoun M., et al. Hepcidin, a new iron regulatory peptide. Blood cells, molecules & diseases,2002,29(3):327-335.
[71]. Nemeth E., Tuttle M.S., Powelson J., et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science (New York, N.Y, 2004,306(5704):2090-2093.
[72]. Santos M., Clevers H., de Sousa M., et al. Adaptive response of iron absorption to anemia, increased erythropoiesis, iron deficiency, and iron loading in beta2-microglobulin knockout mice. Blood,1998,91(8):3059-3065.
[73]. Pigeon C., Ilyin G, Courselaud B., et al. A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. The Journal of biological chemistry,2001,276(11): 7811-7819.
[74]. Wang Q., Du F., Qian Z.M., et al. Lipopolysaccharide induces a significant increase in expression of iron regulatory hormone hepcidin in the cortex and substantia nigra in rat brain. Endocrinology,2008,149(8):3920-3925.
[75]. Lee P., Peng H., Gelbart T., et al. Regulation of hepcidin transcription by interleukin-1 and interleukin-6. Proceedings of the National Academy of Sciences of the United States of America,2005,102(6):1906-1910.
[76]. Nemeth E., Rivera S., Gabayan V., et al. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. The Journal of clinical investigation,2004,113(9):1271-1276.
[77]. Pak M., Lopez M.A., Gabayan V., et al. Suppression of hepcidin during anemia requires erythropoietic activity. Blood,2006,108(12):3730-3735.
[78]. Origa R., Galanello R., Ganz T., et al. Liver iron concentrations and urinary hepcidin in beta-thalassemia Haematologica,2007,92(5):583-588.
[79]. Huang F.W., Pinkus J.L., Pinkus G.S., et al. A mouse model of juvenile hemochromatosis. The Journal of clinical investigation,2005,115(8):2187-2191.
[80]. Santos P.C., Cancado R.D., Pereira A.C., et al. Hereditary hemochromatosis: Mutations in genes involved in iron homeostasis in Brazilian patients. Blood cells, molecules & diseases.46(4):302-307.
[81]. Merle U., Fein E., Gehrke S.G., et al. The iron regulatory peptide hepcidin is expressed in the heart and regulated by hypoxia and inflammation. Endocrinology, 2007,148(6):2663-2668.
[82]. Simonis G, Mueller K., Schwarz P., et al. The iron-regulatory peptide hepcidin is upregulated in the ischemic and in the remote myocardium after myocardial infarction. Peptides.31(9):1786-1790.
[83]. Maruna P., Vokurka M. and Lindner J. Plasma hepcidin correlates positively with interleukin-6 in patients undergoing pulmonary endarterectomy. Physiological research/Academia Scientiarum Bohemoslovaca.
[84]. Valenti L., Dongiovanni P., Motta B.M., et al. Plasma hepcidin and macrophage iron correlate with MCP-1 release and vascular damage in patients with metabolic syndrome alterations. Arteriosclerosis, thrombosis, and vascular biology.31(3): 683-690.
[85]. Badimon L., Storey R.F. and Vilahur G. Update on lipids, inflammation and atherothrombosis. Thrombosis and haemostasis, (Suppl.1).
[86]. Evangelopoulos A.A., Vallianou N.G., Bountziouka V., et al. Association between plasma cystatin C, monocytes and other inflammatory markers. Internal medicine journal.