载脂蛋白A5基因多态性与老年高血压的关联性研究
|
摘要
目的
研究载脂蛋白A5基因(APOA5)-1131T/C多态性在正常健康人群和老年高血压患者中的基因频率和等位基因频率分布情况,探讨-1131T/C多态性对血浆脂质代谢、动脉弹性的影响及其与老年高血压风险性之间的关系,了解其在老年高血压发生过程中的作用,并探讨其在老年高血压发生中的机制。
方法
采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)结合琼脂糖凝胶电泳技术(AGE),对随机选择的非亲属青岛地区汉族老年高血压患者130例(平均年龄71.24±5.72岁),以及年龄和性别相匹配的健康体检者120例为对照组(平均年龄70.49±6.43岁),检测了APOA5基因-1131T/C多态性基因型和等位基因的分布;同时采用生化方法检测了研究对象的血脂水平;应用彩色多普勒超声诊断仪测定右颈总动脉内膜中层厚度(IMT)、收缩末期内径(Ds)、舒张末期内径(Dd),计算压力应变弹性系数(EP)、僵硬系数(β)、动脉顺应性(AC)。
结果
老年高血压组和对照组两组人群中APOA5基因-1131T/C多态性基因型频率存在明显差异(P=0.014),老年高血压组APOA5 -1131C等位基因频率明显高于对照组(0.419比0.296,P= 0.004)。C基因携带者(TC+CC基因型)患高血压的风险是TT基因型的2.03倍(95%CI:1.21～3.39),经校正年龄、性别、体重指数、吸烟史、饮酒、高血压家族史及血清HDL-C、LDL-C水平等相关影响因素,其差异仍具有统计学意义(OR=1.65 95%CI:1.04～2.61);老年高血压组APOA5基因-1131T/C多态性不同基因型亚组间的TG水平差异有统计学意义(P<0.01),CC、TC组明显高于TT组,而CC组的TG水平最高;其他血脂指标差异无统计学意义(P>0.05);老年高血压组的EP、β、IMT均明显高于对照组,而AC明显低于对照组(P<0.01),无论老年高血压组还是对照组中,三种基因型的EP、β、AC、IMT差异均无统计学意义(P>0.05)。
结论
本研究证实APOA5基因可能是高血压的候选基因;APOA5基因-1131位点T/C多态性为老年高血压的遗传标记,-1131C等位基因可能与老年高血压的发生相关联, APOA5基因-1131T/C多态性对人群血清TG水平有重要影响,与EP、β、AC、IMT无明显关联。
Objective
To investigate the distribution of apolipoprotein A5 (APOA5) gene -1131T/C polymorphism in the Han population in Qingdao, and to explore its effects on lipid metabolism and artery elasticity, and the association between susceptibility to elderly hypertension and the -1131T/C polymorphism in the APOA5 gene.
Methods
Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and agarose gelelectrophoresis (AGE) methods, we analyzed the genotypes and alleles in 130 elderly patients with essential hypertension (mean age 71.24±5.72years) and 120 healthy controls (mean age 70.49±6.43 years).
The levels of serum lipid profiles were studied by biochemicalmethods. Using color doppler ultrasound we measured systolic inner diameter (Ds), diastolic inner diameter (Dd) and intima-media thickness (IMT) of the right common carotid artery (RCCA) and calculated pressure-strain elastic modulus (Ep), stiffness (β) and the arterial compliance (AC). Results
The frequency of APOA5 -1131TT, TC, CC genotypes were distinctlydifferent between groups of elderly patients with essential hypertension andcontrol (P=0.014). The frequency of the APOA5 -1131 C allele in elderly hypertensive patients was significantly higher than that of the controlgroup (0.419 vs 0.296 P=0.004).Compared with the wild type TT, TC heterozygote+CC homozygote had a significantly increased elderly hypertensionrisk (OR =2.03 and OR=1.65 using unadjusted and adjusted logistic regression models,respectively).This association still existed after adjustment for the sex, age, BMI, smoking, alcohol, hypertensive familial history and the levels of serumHDL-C and LDL-C.APOA5 -1131TT, TC, CC genotypes al-so showed a co-rrelation with plasma TG levels in elderly hypertensive pat-ients (P<0.01).The -1131C allele contributed to the increase of serum levels of TG but had no effect on profiles of TC, HDL-C, LDL-C in elderlyhypertensive pa-tients.In the elderly hypertensive group, the serumlevels of TG of CC ge-notype were significantly higher than those of TT genotype and TC genot-ype.The serum levels of TG of TC genotype was higher than that of TT genotype.Compared with the normal group,data of Ep,βweresignificantly hi-gher in hypertension group(P<0.01),while AC was obviouslylower(P<0.01). However, there was no significance in profiles of IMT, Ep,βand AC in va-rious genotypes in both groups.
Conclusions
The APOA5 -1131T/C polymorphism might contribute to an increased risk of elderly hypertension among Chinese accompanied by an elevation of serum TG levels. The APOA5 -1131T/C polymorphism was not related with artery elasticity.
研究载脂蛋白A5基因(APOA5)-1131T/C多态性在正常健康人群和老年高血压患者中的基因频率和等位基因频率分布情况,探讨-1131T/C多态性对血浆脂质代谢、动脉弹性的影响及其与老年高血压风险性之间的关系,了解其在老年高血压发生过程中的作用,并探讨其在老年高血压发生中的机制。
方法
采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)结合琼脂糖凝胶电泳技术(AGE),对随机选择的非亲属青岛地区汉族老年高血压患者130例(平均年龄71.24±5.72岁),以及年龄和性别相匹配的健康体检者120例为对照组(平均年龄70.49±6.43岁),检测了APOA5基因-1131T/C多态性基因型和等位基因的分布;同时采用生化方法检测了研究对象的血脂水平;应用彩色多普勒超声诊断仪测定右颈总动脉内膜中层厚度(IMT)、收缩末期内径(Ds)、舒张末期内径(Dd),计算压力应变弹性系数(EP)、僵硬系数(β)、动脉顺应性(AC)。
结果
老年高血压组和对照组两组人群中APOA5基因-1131T/C多态性基因型频率存在明显差异(P=0.014),老年高血压组APOA5 -1131C等位基因频率明显高于对照组(0.419比0.296,P= 0.004)。C基因携带者(TC+CC基因型)患高血压的风险是TT基因型的2.03倍(95%CI:1.21～3.39),经校正年龄、性别、体重指数、吸烟史、饮酒、高血压家族史及血清HDL-C、LDL-C水平等相关影响因素,其差异仍具有统计学意义(OR=1.65 95%CI:1.04～2.61);老年高血压组APOA5基因-1131T/C多态性不同基因型亚组间的TG水平差异有统计学意义(P<0.01),CC、TC组明显高于TT组,而CC组的TG水平最高;其他血脂指标差异无统计学意义(P>0.05);老年高血压组的EP、β、IMT均明显高于对照组,而AC明显低于对照组(P<0.01),无论老年高血压组还是对照组中,三种基因型的EP、β、AC、IMT差异均无统计学意义(P>0.05)。
结论
本研究证实APOA5基因可能是高血压的候选基因;APOA5基因-1131位点T/C多态性为老年高血压的遗传标记,-1131C等位基因可能与老年高血压的发生相关联, APOA5基因-1131T/C多态性对人群血清TG水平有重要影响,与EP、β、AC、IMT无明显关联。
Objective
To investigate the distribution of apolipoprotein A5 (APOA5) gene -1131T/C polymorphism in the Han population in Qingdao, and to explore its effects on lipid metabolism and artery elasticity, and the association between susceptibility to elderly hypertension and the -1131T/C polymorphism in the APOA5 gene.
Methods
Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and agarose gelelectrophoresis (AGE) methods, we analyzed the genotypes and alleles in 130 elderly patients with essential hypertension (mean age 71.24±5.72years) and 120 healthy controls (mean age 70.49±6.43 years).
The levels of serum lipid profiles were studied by biochemicalmethods. Using color doppler ultrasound we measured systolic inner diameter (Ds), diastolic inner diameter (Dd) and intima-media thickness (IMT) of the right common carotid artery (RCCA) and calculated pressure-strain elastic modulus (Ep), stiffness (β) and the arterial compliance (AC). Results
The frequency of APOA5 -1131TT, TC, CC genotypes were distinctlydifferent between groups of elderly patients with essential hypertension andcontrol (P=0.014). The frequency of the APOA5 -1131 C allele in elderly hypertensive patients was significantly higher than that of the controlgroup (0.419 vs 0.296 P=0.004).Compared with the wild type TT, TC heterozygote+CC homozygote had a significantly increased elderly hypertensionrisk (OR =2.03 and OR=1.65 using unadjusted and adjusted logistic regression models,respectively).This association still existed after adjustment for the sex, age, BMI, smoking, alcohol, hypertensive familial history and the levels of serumHDL-C and LDL-C.APOA5 -1131TT, TC, CC genotypes al-so showed a co-rrelation with plasma TG levels in elderly hypertensive pat-ients (P<0.01).The -1131C allele contributed to the increase of serum levels of TG but had no effect on profiles of TC, HDL-C, LDL-C in elderlyhypertensive pa-tients.In the elderly hypertensive group, the serumlevels of TG of CC ge-notype were significantly higher than those of TT genotype and TC genot-ype.The serum levels of TG of TC genotype was higher than that of TT genotype.Compared with the normal group,data of Ep,βweresignificantly hi-gher in hypertension group(P<0.01),while AC was obviouslylower(P<0.01). However, there was no significance in profiles of IMT, Ep,βand AC in va-rious genotypes in both groups.
Conclusions
The APOA5 -1131T/C polymorphism might contribute to an increased risk of elderly hypertension among Chinese accompanied by an elevation of serum TG levels. The APOA5 -1131T/C polymorphism was not related with artery elasticity.
引文
[1] Safar ME,Siche SP,Mallion JM,et al. Arterial mechanics predict cardiovascular risk in hypertension [J]. J Hypertens, 1997; 15: 1605-1611.
[2] Cohn JN.Vascular wall function as a risk marker for cardiovascular disease [J].J hypertens, 1999, 17 Suppl 5: s41-44
[3] Zavaroni, Bonini L, Gasparini P, et al. Hyperinsulinemia in a normal popution as a predictor of non-insulin-dependent diabetes mellitus,hyperte nsion,andcoronary heart disease:the Barilla factory revisited [J].Metab -olism, 1999, 48: 989-99403 361:1629-1641
[4] Vu-Dac N,Gervois P,Jakel H,et al. Apolipoprotein A5,a crucial determinant of plasma triglyceride levels, is highly responsive to peroxisome proliferator-activated receptor alpha activators[J].J Biol Chem,2003, 278(20):17982-17985.
[5] Staessen JA, Wang J, Bianchi G.Essential hypertension[J].Lancet, 2003,3 61:1629 - 1641.
[6] van der Vliet HN, Sammels MG, Leegwater AC, et al. Apolipoprotein A-V: a novel apolipoprotein associated with an early phase of liver regeneration [J]. J Biol Chem, 2001,276(48): 44 512-520
[7] Pennacchio LA, Olivier M, Hubacek JA, et al.An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing [J].Science, 2001,294(5540): 169-173
[8] Binder A. Identification of genes for a complex trait:examples from hypertension [J]. Curr Pharm Biotechnol, 2006, 7(1): 1-13.
[9] Mondry A, Loh M, Liu P,t al.Polymorphisms of the insertion/deletion ACE and M235T AGT genes and hypertension: surprising new findings and meta-analysis of data [J]. BMC Nephrol, 2005, 6(1): 1-4.
[10] van der Vliet HN, Schaap FG, Levels JH, et al. Adenoviral overexpression of apolipoproteion A-V reduces serum levels of triglycerides and cholesterol in mice[J].Biochem Biophys Res Commun,2002,295:1156-1159
[11] Pennacchio LA, Olivier M, Hubacek JA, et al. Two independent Apolipoprotein A5 haplotypes influence human plasma triglyceride levels [J].Hum Mol Genet,2002,11(24): 3031-3038.
[12] Endo K, Yanagi H ,Araki J,et al.Association found between the promotor region polymorphism in the apolipoprotein A-V gene and serumtriglyceride level in Japanese school children[J]. Hum Genet, 2002, 111(6): 570-572
[13] Lai CQ, Tai ES, Tan CE, et al. The apolipoprotein A5 locus is a strong determinant of plasma triglyceride concentrations across ethnic groups in Singapore[J]. J Lipid Res, 2003, 44: 2365-2373
[14] Baum L, Tomlinson B, Thomas GN. APOA5-1131T/C polymorphism is associated with triglyceride levels in Chinese men[J].Clin Genet, 2003,63: 377-379
[15] Nabika T, Nasreen S, Kobayashi S,et al.The genetic effect of the aplipoprotein AV gene on the serum triglyceride level in Japanese[J]. Atherosclerosis,2002,165:201-204
[16] Jang Y, Kim JY, Kim OY,et al The-113lT/C polymorphism in the aplipoprotein A5 gene is associated with postprandial hypertriacylglycer- omia elevated small, dense LDL concentrations and oxidative stress in nonobese Korean men[J]. Am J Clin Nutr, 2004, 80: 832-840
[17] Hubaeek JA, Adamkova V,Ceska R,et al. New variants in the apolipoprote- in AV gene in individuals with extreme triglyceride level[J]. Physiol Res,2004,53: 225-228
[18] Klos KL, Hamon S, Clark AC, et al. APOA5 polymorphisms influence plasma triglycerides in young, healthy African Americans and whites of the CARDIA Study[J]. J Lipid Res, 2005, 46: 564-571.
[19] Hodoglugil U, Tanyolac S, Williameon DW, et al. Apolipoprotein A-V: apotential modulator of plasma triglyceride levels in Turka[J].J Lipid Res, 2006, 47:144-153.
[20] Ribalta J, Figuera L, Fernandez-Ballart J,et al.Newly identified apolipoprotein AV gene predisposes to high plasma triglycerides in familial combined hyperlipidemia[J]. Clin Chem, 2002,48(9): 1 597-600
[21] Talmud PJ, Hawe E, Martin S, et al. Relative contribution of variation within the APOC3/A4/A5 gene cluster in determining plasma triglycerid es [J].HumMol Genet, 2002, 11(24): 3 039-046
[22] Khovidhunkit W, Duchateau PN, Medzihradszky KF,et al.Apolipoproteins A-IV and A-V are acute-phase proteins in mouse HDL[J].Atherosclerosis, 2004,176: 37-44.
[23]卢漫,唐红,黄鹤.血管回声跟踪技术对高血压病患者早期颈动脉硬化的研究[J].中华超声影像学杂志,2005,14(9):713-714
[24] Fruchart-Najib J, Bauge E, Niculescu LS, et al. Mechanism of triglyceride lowering in mice expressing human apolipoprotein A5[J].Biochem Biophys Res Commun, 2004, 319(2): 397-404
[25] Merkel M, Loeffler B, KlugerM, et al. Apolipoprotein AV accelerates plasmah-ydrolysis of triglyceride-rich lipoproteins by interaction with proteogly canboundlipoproteinlipase[J].BiolChem,2005,280(22):21553 -21560.
[26] Baroukh N, Bauge E, Akiyama J,et al. Analysis of apolipoprotein A5, C3, and plasma triglyceride concentrations in genetically engineered mice[J]. Arterioscler Thromb Vasc Biol, 2004, 24(7): 1297-1302.
[27] Schaap FG,Rensen PC,Voshol PJ, et al. ApoAV reduces plasm triglycerides by inhibiting very low density lipoproteintriglyceride (VLDL-TG) roducti- on and stimulating lipoprotein lipase mediated VLDL-TG hydrolysis[J].J Biol Chem,2004,279(27): 27941 -27947.
[28] van Dijk KW,Rensen PC,Voshol PJ, et al. The role and mode of action of apolipoproteins CIII and AV:synergistic actors in triglyceride metabolism? [J]. Curr Opin Lipidol,2004,15(3):239-246.
[29] Grosskopf I,Baroukh N,Lee SJ.Apolipoprotein A-V deficiency results in marked hypertriglyceridemia attributable to decreased lipolysis of triglycer -iderichlipoproteins and removal of their remnants [J] .Arterioscler Thromb Vasc Biol ,2005, 25(12): 2573-2579.
[30] Nilsson SK, Lookene A, Beckstead JA, et al. Apolipoprotein A-V interaction with members of the low density lipoprotein receptor gene family [J]. Biochemistry, 2007, 46(12): 3 896-904
[31] Jakel H,Nowak M, Moitrot E, et al. The liver X receptor ligand T0901317 down-regulates APOA5 gene expression through activation of SREBP-1c[J].JBiol Chem, 2004, 279(44): 45462-45469.
[32] owak M, Helleboid-Chapman A,akel H,t al.nsulin-mediated down-reglaton of Apolipoprotein A5 gene expression through the phosphatidylinositol 3-kinase pathway:role of upstream stimulatory factor[J].Mol Cell Biol, 2005, 25(4): 1537-1548.
[1] vander Vliet HN, Sammels MG, Leegwater AC, et al.polipoprotein A-V:a novel apolipoprotein associated with an early phase of liver regeneration [J]. Biol Chem, 2001,276(48): 44 512-520
[2] Pennacchio LA,livier M,ubacek JA, al. An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing[J]. cience,2001,294(5540):169-173
[3] Beckstead JA,Oda MN, Martin DD,et al.Structure-function studies of human apolipoprotein A-V: a regulator of plasma lipid homeostasis[J]. Biochemistry,2003, 42 (31):9 416-9 423.
[4] Weinberg RB,Cook VR,Beckstead JA,et al. Structure and interfacial properties of human apolipoprotein A-V[J].J Biol Chem,2003,278(36):34 438-34 444.
[5] Talmud PJ.Rare APOA5 mutations-Clinical consequences,metabolic and functional effects [J].Atherosclerosis, 2007,194(2): 287-292.
[6] Sun GT, Bi N, Li GP, et al. Identification of lipid binding and lipoprotein lipase activation domains of human apoAV [J].J Chem Phys Lip, 2006, 143(1-2): 22-28.
[7] van der Vliet HN, Schaap FG, Levels JH, et al. Adenoviral overexpression of apolipoproteion AV reduces serum levels of triglycerides and cholesterol in mice [J].BiochemBiophys Res Commun, 2002,295:1156-1159
[8] Wei Huang, Nan Bi,Xiaohong Zhang,et al.Overexpression of apolipoproteinAV in the liver reduces plasma triglyceride and cholesterol but not HDL in ApoE deficient mice [J].Biochemical and Biophysical Research Communications,2006, 346: 14-18.
[9] Khovidhunkit W,Duchateau PN,Medzihradszky KF,et al.Apolipoproteins ApoAⅣand APOAⅤare acute-phase proteins in mouse HDL [J]. Atheros- clerosis,2004,176:37-44.
[10] Becker S,Schomburg L,Renko K,et al. Altered apolipoprotein A-V expression during the acute phase response in independent of plasma triglycerid levels in mice and humans [J].Biochemical and Biophysical Research Commu-nications,2006,339:833-839.
[11] Vaessen SFC, Schaap FG, Kuivenhoven JA, et al. Apolipoprotein AV, triglycerides and risk of coronary artery disease: the prospective Epic -Norfolk population study [J].Journal of lipid Research,2006,47:2064 -2070.
[12] Talmud PJ, Cooper JA, Hattori H,et al.The apolipoprotein AⅤgenotypeand plasma apolipoprotein AⅤand triglyceride levels: prospective risk of type2 diabetes.Result from the Northwick Park Heart StudyⅡ[J]. Diabetologia,2006,49:2337-2340.
[13] Ishihara M, Kujinaoka T, Tuasaki T,et al. A sandwich enzyme-linked immunosorb-entassay for human plasma apolipoprotein A-V concentration [J].Lipid Res, 2005,46 (9):2015-2022
[14] Henneman P,Schaap FG,Havekes LM,et al.Plasma APOA5 levels are markedly elevated in severe hypertriglyceridemia and positively correlated with theAPOA5 S19W polymorphism [J].Atherosclerosis,2007,193(1): 129-134.
[15]Pennacchio LA,Olivier M,ubacek JA,t al.Two independent Apolipoprotein A5 haplotypes influence human plasma triglyceride levels [J].Hum Mol Genet,2002,11 (24):3031-3038.
[16] Wung SF,Aouizerat BE.Gender and ethnic differences in a case-control sudy of dyslipidemia:using the apolipoprotein AⅤgene as an example in cardi-ovascular genetics [J].Res Theory Nurs Prac,t 2003,17(4):281-299.
[17]毕楠,鄢盛恺,李国平等.冠心病患者载脂蛋白A5和载脂蛋白C3基因多态性的研究[J].中华心血管病杂志,2005,33(2):116-121
[18]李国平,王建跃,鄢盛恺等.人载脂蛋白A5基因多态性56C→G与血浆甘油三酯的关系[J].中国动脉硬化杂志,2004,12(5):574-576.
[19] Lai CQ, Tai ES, Tan CE, et al. The apoAⅤlocus is a strong determinant of plasma triglyceride concentrations across ethnic groups in Singapore [J].JLipid Res,2003, 44 (12):2365-2373.
[20] Kao JT,Wen HC,Chien KL,et al.A novel genetic variant in the Apolipoprotein A5 gene is associated with hypertriglyceridemia[J].Hum Mol Genet, 2003,12(19):2533-2539.
[21] Tang YB,Sun P,Guo DP,et al.A genetic variant c.553G>T in the apolipoprotein A5 gene is associated with an increased risk of coronary artery diseaseand altered triglyceride levels in a Chinese population [J]. Atherosclerosis,2006,185(2):433-437.
[22]刘合焜,王春婷,张思仲等.APOA5基因单核苷酸多态性与冠心病相关性研究[J].中华医学遗传学杂志,2004,21(4):335-338.
[23] Olofsson SO.ApoA-V:the regulation of a regulator of plasma triglycerides [J]. Arterioscler Thromb Vasc Biol,2005,25(6):1 097-099.
[24]毕楠,陈保生.脂蛋白代谢中活性蛋白的结构与功能[M].北京:中国协和医科大学,2005:1-80.
[25] Schaap FG,Rensen PC,Voshol PJ, et al. ApoAV reduces plasma triglycerid -es by inhibiting very low density lipoprotein-triglyceride (VLDL-TG) productionand stimulating lipoprotein lipase-mediated VLDL-TG hydroly- sis [J].Biol Chem, 2004, 279(27): 27941-27947.
[26] Grosskopf I, Baroukh N, Lee SJ. Apolipoprotein A-V deficiency resule in marked hypertriglyceridemia attributable to decreased lipolysis of triglyceride-rich lipoproteins and removal of their remnants [J].Arteriosc- ler Thromb Vasc Bio,l2005, 25(12): 2573-2579.
[27] Fruchart-Najib J,Bauge E,NiculescuLS,et al.Mechanism of triglyceride lowering in mice expressing human apolipoprotein A5 [J].Biochem Biophys ResCommun ,2004 ,319 (5):397-404.
[28] Merkel M, Loeffler B, KlugerM, et al. Apolipoprotein AV accelerates plasma hydrolysis of triglyceride-rich lipoproteins by interaction with proteoglycan bound lipoprotein lipase [J].BiolChem,2005,280(22): 21553 -21560.
[29] Marcais C,Verges B,Charriere S.APOA5 Q139X truncation predisposes to late onset hyperchylomicronemia due to lipoprotein lipase impairment[J].Clin Invest ,2005, 115: 2862-2869.
[30] Oliva CP,Pisciotta L,LiVolti G,et al. Inherited apolipoprotein A-V deficie- ncy in severe hypertriglyceridemia [J].Arterioscler Thromb Vasc Bio,l 2005, 25(2): 411-417.
[31] Lookene A,Beckstead JA,Nilsson S,et al.Apolipoprotein A-V-heparin interactions: implications for plasma lipoprotein metabolism[J].J Biol Chem,2005, 280:25383-25387.
[32] Nilsson SK, Lookene A, Beckstead JA, et al. Apolipoprotein A-V interaction with members of the low density lipoprotein receptor gene family [J].Biochemistry, 2007,46(12): 3 896-904.
[33] Baroukh N,Bauge E, Akiyama J,et al. Analysis of apolipoprotein A5,C3,and plasma triglyceride concentrations in genetically engineered mice.Arterioscler[J]. Thromb Vasc Biol, 2004, 24(7):1297-1302.
[34] Qu S, Perdomo G, Su DG, et al. Effects of apoA-V on HDL and VLDL metabolism in APOC3 transgenic mice [J].J Lipid Res, 2007,48(7): 1 476-487.
[35] Schultze AE,Alborn WE,Newton RK, et al. Administration of a PPARαagonist increases serum apolipoprotein A-V levels and the apolipoprotein A-V/ apolipoprotein C-III ratio [J].Lipid Res, 2005,46(8): 1 591-595.
[36] Vu-Dac N,Gervois P,Jakel H,et al. Apolipoprotein A5,a crucial determinant of plasma triglyceride levels,is highly responsive to peroxisome proliferators-activated receptorαactivators [J]. J Biol Chem,2003,278 (20):17 982-17 985.
[37] Genoux A,Dehondt H,Helleboid-Chapman A,et al .Transcriptional regulat- ion of apolipoprotein A5 gene expression by the nuclear receptor RORα[J].Arterioscler Thromb Vasc Bio,l 2005, 25: 1186-1192.
[38] Lind U, Nilsson T, McPheat J, et al. Identification of the human ApoAV gene as a novel RORa target gene [J].J Biochem Biophys Res Commun, 2005,330(1): 233-241.
[39] Jakel H, Nowak M, Moitrot E, et al. The liver X receptor ligand T0901317 down-regulates APOA5 gene expression through activation of SREBP-1c[J].J Biol Chem, 2004, 279(44): 45462-45469.
[40] Nowak M,Helleboid-Chapman A,Jakel H,et al.Insulin-mediated down-regu- lation of Apolipoprotein A5 gene expression through the phosphatidylinos-itol 3-kinase pathway: role of upstream stimulatory factor[J]. Mol Cell Biol, 2005, 25(4):1537-1548.
[41] Prieur X, Schaap FG, Coste H, et al. Hepatocyte nuclear factor-4a regulates the human apolipoprotein AV gene: identification of a novel response element and involvement in the control by peroxisome proliferator -activatedreceptor–γcoactivator- 1α,AMP-activated protein kinase,and mitogen-activated protein kinase pathway [J].Mol Endocrinol, 2005,19(12): 3 107-125.
[42] Talmud PJ, Hawe E, Martin S,et al. Relative contribution of variation within the APOC3/A4/A5 gene cluster in determining plasma triglycer -ides[J].HumMol Genet,2002,11:3 039-046
[43] Klos KL, Hamon S, Clark AG, et al. APOA5 polymorphisms influence plasma triglycerides in young, healthy AfricanAmericans and whites of the CARDIA Study [J].J Lipid Res, 2005,46(3): 564-571
[44] Nabika T, Nasreen S, Kobayashi S, et al. The genetic effect of the apoprotein AV gene on the serum triglyceride level in Japanese[J]. Athero- sclerosis,2002,165:201-204
[45] Endo K,Yanagi H,Araki J,et al. Association found between the promotereg- ion polymorphism in the apolipoprotein AⅤgene and the serum triglycer- ide level in Japanese schoolchildren [J].Hum Gene,t 2002, 111(6):570-5 72.
[46] Baum L,Tomlinson B,Thomas GN.APOA5-1131T/C polymorphism is associated with triglyceride levels in Chinese men [J]. Clin Genet 2003, 63(5): 377-379.
[47] Li GP,Wang JY,Yan SK, et al. Genetic effect of two polymorphisms in the apolipoprotein A5 gene and apolipoprotein C3 gene on serum lipids and lipoproteins levels in a Chinese population[J].Clin Genet, 2004, 65(6): 470-476
[48] Martin S, Nicaud V, Humphries SE, et al. Contribution of APOA5 gene variants to plasma triglyceride determination and to the response to both fat and glucose tolerance challenges[J]. Biochim Biophys Acta, 2003,1 637: 217-225
[49] Ribalta J,Figuera L,Fernandez-Ballart J,et al.Newly identified apolipopro- tein AV gene predisposes to high plasma triglycerides in familial combinedhyperlipidemia[J].Clin Chem,2002,48:1597-1600
[50] Mar R,Pajukanta P,AllayeeH, et al. Association of the apolipoprotein A1/C3/A4/A5 gene cluster with triglyceride levels and LDL particle size in familial combined hyperlipidemia[J].Circ Res, 2004, 94(7): 993-999.
[51] Aouizerat BE,Kulkarui M,Heilbron D, et al.Genetic analysis of a polymorphism in the human apolipoprotein AV gene, effect or plasma lipids[J].LipidsRes,2003, 44: 1167 -1173.
[52] Austin MA, Talmud PJ, Farin FM, et al. Association of Apolipoprotein A5 variants with LDL particle size and triglyceride in JapaneseAmericans [J]. Biochim Biophys Acta, 2004, 1688(1): 1-9.
[53] Hsu LA, Ko YL, Chang C,h,et al. Genetic variations of apolipoprotein A5 gene is associated with the risk of coronary artery disease Chinese in Taiwan[J]. Atherosclerosis, 2006;143-149.
[54] Liu H,Zhang S, Lin J,et al. Association between DNA variant sites in the apolipoprotein A5 gene and coronary heart disease in Chinese[J]. Metabolism,2005,54 (5):568-572.
[55] Hubacek JA, Skodova Z,Adamkova V, et al. The influence of apoAⅤpolymorphisms (T-1131>C and S19>W) on plasma triglyceride levels and risk of myocardial infarction[J].Clin Genet ,2004, 65(2): 126-130.
[56] Szalai C, Keszei M, Duba J, et al. Polymorphism in the promoter region of the apolipoprotein A5 gene is associated with an increased susceptibility for coronary artery disease [J].Atherosclerosis,2004,173(1): 109-114
[57] Jang Y,Kim JY,Kim OY, et al.The-1131T-->C polymorphism in the apolipoprotein A5 gene is associated with postprandial hypertriacylglycer- olemia;elevated small dense LDL concentration;and oxidative stress in nonobese Koreanmen [J]. AmJ Clin Nutr, 2004, 80(4): 832-840.
[58]Talmud PJ,Martin S,Taskinen MR,et al.APOA5 gene variants, lipoprotein -particle distribution, and progression of coronary heart disease:results from theLOCAT study[J].J Lipid Res,2004,45(4):750-756.
[59] Lai CQ,Demissie S,Cupples LA,et al.Influence of the APOA5 locus on plasma triglyceride,lipoprotein subclasses,and CVD risk in the Framingham HeartStudy [J]. J Lipid Res, 2004, 45(11): 2096-2105.
[60] Lee KW, Ayyobi AF, Frohlich JJ, et al. APOA5 gene polymorphismmo- dulates levels of triglyceride, HDL cholesterol and FERHDL but is not arisk factor for coronary artery disease [J].Atherosclerosis, 2004,176(1): 165-172
[61] Chiu KC,Chiu YF,Boyad-Jian AA.et al.Impact of apolipoprotein A5 polymorphisms on insulin sensitivity and betacell function [J].Pancreas, 2005,30(4):328-332
[62] Yan SK,Cheng XQ,Song YH, et al. Apolipoprotein A5 gene polymorphism -1131T/C: association with plasma lipids and type 2 diabetes mellitus with coronary heart disease in Chinese[J].Clin Chem Lab Med,2005,43(6): 607-612.
[63] Bi N,Yen sk,Li GD,et al. A singhe nucleotole polymorphism -1131T→C in the apolipoprotein A5 gene is associated with increased risk of coronary artery disease and alters triglyceride metabolism in Chinese[J]. Mol Genet Metab,2004,83:280-286.
[64] Esteve E,Faure E,Calvo F, et al.SNP3 polymorphism in apo A-V gene isassociated with small dense LDL particles in TyPe 2 diabetes[J].Diabet- ologia,2004,47:355-356·
[2] Cohn JN.Vascular wall function as a risk marker for cardiovascular disease [J].J hypertens, 1999, 17 Suppl 5: s41-44
[3] Zavaroni, Bonini L, Gasparini P, et al. Hyperinsulinemia in a normal popution as a predictor of non-insulin-dependent diabetes mellitus,hyperte nsion,andcoronary heart disease:the Barilla factory revisited [J].Metab -olism, 1999, 48: 989-99403 361:1629-1641
[4] Vu-Dac N,Gervois P,Jakel H,et al. Apolipoprotein A5,a crucial determinant of plasma triglyceride levels, is highly responsive to peroxisome proliferator-activated receptor alpha activators[J].J Biol Chem,2003, 278(20):17982-17985.
[5] Staessen JA, Wang J, Bianchi G.Essential hypertension[J].Lancet, 2003,3 61:1629 - 1641.
[6] van der Vliet HN, Sammels MG, Leegwater AC, et al. Apolipoprotein A-V: a novel apolipoprotein associated with an early phase of liver regeneration [J]. J Biol Chem, 2001,276(48): 44 512-520
[7] Pennacchio LA, Olivier M, Hubacek JA, et al.An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing [J].Science, 2001,294(5540): 169-173
[8] Binder A. Identification of genes for a complex trait:examples from hypertension [J]. Curr Pharm Biotechnol, 2006, 7(1): 1-13.
[9] Mondry A, Loh M, Liu P,t al.Polymorphisms of the insertion/deletion ACE and M235T AGT genes and hypertension: surprising new findings and meta-analysis of data [J]. BMC Nephrol, 2005, 6(1): 1-4.
[10] van der Vliet HN, Schaap FG, Levels JH, et al. Adenoviral overexpression of apolipoproteion A-V reduces serum levels of triglycerides and cholesterol in mice[J].Biochem Biophys Res Commun,2002,295:1156-1159
[11] Pennacchio LA, Olivier M, Hubacek JA, et al. Two independent Apolipoprotein A5 haplotypes influence human plasma triglyceride levels [J].Hum Mol Genet,2002,11(24): 3031-3038.
[12] Endo K, Yanagi H ,Araki J,et al.Association found between the promotor region polymorphism in the apolipoprotein A-V gene and serumtriglyceride level in Japanese school children[J]. Hum Genet, 2002, 111(6): 570-572
[13] Lai CQ, Tai ES, Tan CE, et al. The apolipoprotein A5 locus is a strong determinant of plasma triglyceride concentrations across ethnic groups in Singapore[J]. J Lipid Res, 2003, 44: 2365-2373
[14] Baum L, Tomlinson B, Thomas GN. APOA5-1131T/C polymorphism is associated with triglyceride levels in Chinese men[J].Clin Genet, 2003,63: 377-379
[15] Nabika T, Nasreen S, Kobayashi S,et al.The genetic effect of the aplipoprotein AV gene on the serum triglyceride level in Japanese[J]. Atherosclerosis,2002,165:201-204
[16] Jang Y, Kim JY, Kim OY,et al The-113lT/C polymorphism in the aplipoprotein A5 gene is associated with postprandial hypertriacylglycer- omia elevated small, dense LDL concentrations and oxidative stress in nonobese Korean men[J]. Am J Clin Nutr, 2004, 80: 832-840
[17] Hubaeek JA, Adamkova V,Ceska R,et al. New variants in the apolipoprote- in AV gene in individuals with extreme triglyceride level[J]. Physiol Res,2004,53: 225-228
[18] Klos KL, Hamon S, Clark AC, et al. APOA5 polymorphisms influence plasma triglycerides in young, healthy African Americans and whites of the CARDIA Study[J]. J Lipid Res, 2005, 46: 564-571.
[19] Hodoglugil U, Tanyolac S, Williameon DW, et al. Apolipoprotein A-V: apotential modulator of plasma triglyceride levels in Turka[J].J Lipid Res, 2006, 47:144-153.
[20] Ribalta J, Figuera L, Fernandez-Ballart J,et al.Newly identified apolipoprotein AV gene predisposes to high plasma triglycerides in familial combined hyperlipidemia[J]. Clin Chem, 2002,48(9): 1 597-600
[21] Talmud PJ, Hawe E, Martin S, et al. Relative contribution of variation within the APOC3/A4/A5 gene cluster in determining plasma triglycerid es [J].HumMol Genet, 2002, 11(24): 3 039-046
[22] Khovidhunkit W, Duchateau PN, Medzihradszky KF,et al.Apolipoproteins A-IV and A-V are acute-phase proteins in mouse HDL[J].Atherosclerosis, 2004,176: 37-44.
[23]卢漫,唐红,黄鹤.血管回声跟踪技术对高血压病患者早期颈动脉硬化的研究[J].中华超声影像学杂志,2005,14(9):713-714
[24] Fruchart-Najib J, Bauge E, Niculescu LS, et al. Mechanism of triglyceride lowering in mice expressing human apolipoprotein A5[J].Biochem Biophys Res Commun, 2004, 319(2): 397-404
[25] Merkel M, Loeffler B, KlugerM, et al. Apolipoprotein AV accelerates plasmah-ydrolysis of triglyceride-rich lipoproteins by interaction with proteogly canboundlipoproteinlipase[J].BiolChem,2005,280(22):21553 -21560.
[26] Baroukh N, Bauge E, Akiyama J,et al. Analysis of apolipoprotein A5, C3, and plasma triglyceride concentrations in genetically engineered mice[J]. Arterioscler Thromb Vasc Biol, 2004, 24(7): 1297-1302.
[27] Schaap FG,Rensen PC,Voshol PJ, et al. ApoAV reduces plasm triglycerides by inhibiting very low density lipoproteintriglyceride (VLDL-TG) roducti- on and stimulating lipoprotein lipase mediated VLDL-TG hydrolysis[J].J Biol Chem,2004,279(27): 27941 -27947.
[28] van Dijk KW,Rensen PC,Voshol PJ, et al. The role and mode of action of apolipoproteins CIII and AV:synergistic actors in triglyceride metabolism? [J]. Curr Opin Lipidol,2004,15(3):239-246.
[29] Grosskopf I,Baroukh N,Lee SJ.Apolipoprotein A-V deficiency results in marked hypertriglyceridemia attributable to decreased lipolysis of triglycer -iderichlipoproteins and removal of their remnants [J] .Arterioscler Thromb Vasc Biol ,2005, 25(12): 2573-2579.
[30] Nilsson SK, Lookene A, Beckstead JA, et al. Apolipoprotein A-V interaction with members of the low density lipoprotein receptor gene family [J]. Biochemistry, 2007, 46(12): 3 896-904
[31] Jakel H,Nowak M, Moitrot E, et al. The liver X receptor ligand T0901317 down-regulates APOA5 gene expression through activation of SREBP-1c[J].JBiol Chem, 2004, 279(44): 45462-45469.
[32] owak M, Helleboid-Chapman A,akel H,t al.nsulin-mediated down-reglaton of Apolipoprotein A5 gene expression through the phosphatidylinositol 3-kinase pathway:role of upstream stimulatory factor[J].Mol Cell Biol, 2005, 25(4): 1537-1548.
[1] vander Vliet HN, Sammels MG, Leegwater AC, et al.polipoprotein A-V:a novel apolipoprotein associated with an early phase of liver regeneration [J]. Biol Chem, 2001,276(48): 44 512-520
[2] Pennacchio LA,livier M,ubacek JA, al. An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing[J]. cience,2001,294(5540):169-173
[3] Beckstead JA,Oda MN, Martin DD,et al.Structure-function studies of human apolipoprotein A-V: a regulator of plasma lipid homeostasis[J]. Biochemistry,2003, 42 (31):9 416-9 423.
[4] Weinberg RB,Cook VR,Beckstead JA,et al. Structure and interfacial properties of human apolipoprotein A-V[J].J Biol Chem,2003,278(36):34 438-34 444.
[5] Talmud PJ.Rare APOA5 mutations-Clinical consequences,metabolic and functional effects [J].Atherosclerosis, 2007,194(2): 287-292.
[6] Sun GT, Bi N, Li GP, et al. Identification of lipid binding and lipoprotein lipase activation domains of human apoAV [J].J Chem Phys Lip, 2006, 143(1-2): 22-28.
[7] van der Vliet HN, Schaap FG, Levels JH, et al. Adenoviral overexpression of apolipoproteion AV reduces serum levels of triglycerides and cholesterol in mice [J].BiochemBiophys Res Commun, 2002,295:1156-1159
[8] Wei Huang, Nan Bi,Xiaohong Zhang,et al.Overexpression of apolipoproteinAV in the liver reduces plasma triglyceride and cholesterol but not HDL in ApoE deficient mice [J].Biochemical and Biophysical Research Communications,2006, 346: 14-18.
[9] Khovidhunkit W,Duchateau PN,Medzihradszky KF,et al.Apolipoproteins ApoAⅣand APOAⅤare acute-phase proteins in mouse HDL [J]. Atheros- clerosis,2004,176:37-44.
[10] Becker S,Schomburg L,Renko K,et al. Altered apolipoprotein A-V expression during the acute phase response in independent of plasma triglycerid levels in mice and humans [J].Biochemical and Biophysical Research Commu-nications,2006,339:833-839.
[11] Vaessen SFC, Schaap FG, Kuivenhoven JA, et al. Apolipoprotein AV, triglycerides and risk of coronary artery disease: the prospective Epic -Norfolk population study [J].Journal of lipid Research,2006,47:2064 -2070.
[12] Talmud PJ, Cooper JA, Hattori H,et al.The apolipoprotein AⅤgenotypeand plasma apolipoprotein AⅤand triglyceride levels: prospective risk of type2 diabetes.Result from the Northwick Park Heart StudyⅡ[J]. Diabetologia,2006,49:2337-2340.
[13] Ishihara M, Kujinaoka T, Tuasaki T,et al. A sandwich enzyme-linked immunosorb-entassay for human plasma apolipoprotein A-V concentration [J].Lipid Res, 2005,46 (9):2015-2022
[14] Henneman P,Schaap FG,Havekes LM,et al.Plasma APOA5 levels are markedly elevated in severe hypertriglyceridemia and positively correlated with theAPOA5 S19W polymorphism [J].Atherosclerosis,2007,193(1): 129-134.
[15]Pennacchio LA,Olivier M,ubacek JA,t al.Two independent Apolipoprotein A5 haplotypes influence human plasma triglyceride levels [J].Hum Mol Genet,2002,11 (24):3031-3038.
[16] Wung SF,Aouizerat BE.Gender and ethnic differences in a case-control sudy of dyslipidemia:using the apolipoprotein AⅤgene as an example in cardi-ovascular genetics [J].Res Theory Nurs Prac,t 2003,17(4):281-299.
[17]毕楠,鄢盛恺,李国平等.冠心病患者载脂蛋白A5和载脂蛋白C3基因多态性的研究[J].中华心血管病杂志,2005,33(2):116-121
[18]李国平,王建跃,鄢盛恺等.人载脂蛋白A5基因多态性56C→G与血浆甘油三酯的关系[J].中国动脉硬化杂志,2004,12(5):574-576.
[19] Lai CQ, Tai ES, Tan CE, et al. The apoAⅤlocus is a strong determinant of plasma triglyceride concentrations across ethnic groups in Singapore [J].JLipid Res,2003, 44 (12):2365-2373.
[20] Kao JT,Wen HC,Chien KL,et al.A novel genetic variant in the Apolipoprotein A5 gene is associated with hypertriglyceridemia[J].Hum Mol Genet, 2003,12(19):2533-2539.
[21] Tang YB,Sun P,Guo DP,et al.A genetic variant c.553G>T in the apolipoprotein A5 gene is associated with an increased risk of coronary artery diseaseand altered triglyceride levels in a Chinese population [J]. Atherosclerosis,2006,185(2):433-437.
[22]刘合焜,王春婷,张思仲等.APOA5基因单核苷酸多态性与冠心病相关性研究[J].中华医学遗传学杂志,2004,21(4):335-338.
[23] Olofsson SO.ApoA-V:the regulation of a regulator of plasma triglycerides [J]. Arterioscler Thromb Vasc Biol,2005,25(6):1 097-099.
[24]毕楠,陈保生.脂蛋白代谢中活性蛋白的结构与功能[M].北京:中国协和医科大学,2005:1-80.
[25] Schaap FG,Rensen PC,Voshol PJ, et al. ApoAV reduces plasma triglycerid -es by inhibiting very low density lipoprotein-triglyceride (VLDL-TG) productionand stimulating lipoprotein lipase-mediated VLDL-TG hydroly- sis [J].Biol Chem, 2004, 279(27): 27941-27947.
[26] Grosskopf I, Baroukh N, Lee SJ. Apolipoprotein A-V deficiency resule in marked hypertriglyceridemia attributable to decreased lipolysis of triglyceride-rich lipoproteins and removal of their remnants [J].Arteriosc- ler Thromb Vasc Bio,l2005, 25(12): 2573-2579.
[27] Fruchart-Najib J,Bauge E,NiculescuLS,et al.Mechanism of triglyceride lowering in mice expressing human apolipoprotein A5 [J].Biochem Biophys ResCommun ,2004 ,319 (5):397-404.
[28] Merkel M, Loeffler B, KlugerM, et al. Apolipoprotein AV accelerates plasma hydrolysis of triglyceride-rich lipoproteins by interaction with proteoglycan bound lipoprotein lipase [J].BiolChem,2005,280(22): 21553 -21560.
[29] Marcais C,Verges B,Charriere S.APOA5 Q139X truncation predisposes to late onset hyperchylomicronemia due to lipoprotein lipase impairment[J].Clin Invest ,2005, 115: 2862-2869.
[30] Oliva CP,Pisciotta L,LiVolti G,et al. Inherited apolipoprotein A-V deficie- ncy in severe hypertriglyceridemia [J].Arterioscler Thromb Vasc Bio,l 2005, 25(2): 411-417.
[31] Lookene A,Beckstead JA,Nilsson S,et al.Apolipoprotein A-V-heparin interactions: implications for plasma lipoprotein metabolism[J].J Biol Chem,2005, 280:25383-25387.
[32] Nilsson SK, Lookene A, Beckstead JA, et al. Apolipoprotein A-V interaction with members of the low density lipoprotein receptor gene family [J].Biochemistry, 2007,46(12): 3 896-904.
[33] Baroukh N,Bauge E, Akiyama J,et al. Analysis of apolipoprotein A5,C3,and plasma triglyceride concentrations in genetically engineered mice.Arterioscler[J]. Thromb Vasc Biol, 2004, 24(7):1297-1302.
[34] Qu S, Perdomo G, Su DG, et al. Effects of apoA-V on HDL and VLDL metabolism in APOC3 transgenic mice [J].J Lipid Res, 2007,48(7): 1 476-487.
[35] Schultze AE,Alborn WE,Newton RK, et al. Administration of a PPARαagonist increases serum apolipoprotein A-V levels and the apolipoprotein A-V/ apolipoprotein C-III ratio [J].Lipid Res, 2005,46(8): 1 591-595.
[36] Vu-Dac N,Gervois P,Jakel H,et al. Apolipoprotein A5,a crucial determinant of plasma triglyceride levels,is highly responsive to peroxisome proliferators-activated receptorαactivators [J]. J Biol Chem,2003,278 (20):17 982-17 985.
[37] Genoux A,Dehondt H,Helleboid-Chapman A,et al .Transcriptional regulat- ion of apolipoprotein A5 gene expression by the nuclear receptor RORα[J].Arterioscler Thromb Vasc Bio,l 2005, 25: 1186-1192.
[38] Lind U, Nilsson T, McPheat J, et al. Identification of the human ApoAV gene as a novel RORa target gene [J].J Biochem Biophys Res Commun, 2005,330(1): 233-241.
[39] Jakel H, Nowak M, Moitrot E, et al. The liver X receptor ligand T0901317 down-regulates APOA5 gene expression through activation of SREBP-1c[J].J Biol Chem, 2004, 279(44): 45462-45469.
[40] Nowak M,Helleboid-Chapman A,Jakel H,et al.Insulin-mediated down-regu- lation of Apolipoprotein A5 gene expression through the phosphatidylinos-itol 3-kinase pathway: role of upstream stimulatory factor[J]. Mol Cell Biol, 2005, 25(4):1537-1548.
[41] Prieur X, Schaap FG, Coste H, et al. Hepatocyte nuclear factor-4a regulates the human apolipoprotein AV gene: identification of a novel response element and involvement in the control by peroxisome proliferator -activatedreceptor–γcoactivator- 1α,AMP-activated protein kinase,and mitogen-activated protein kinase pathway [J].Mol Endocrinol, 2005,19(12): 3 107-125.
[42] Talmud PJ, Hawe E, Martin S,et al. Relative contribution of variation within the APOC3/A4/A5 gene cluster in determining plasma triglycer -ides[J].HumMol Genet,2002,11:3 039-046
[43] Klos KL, Hamon S, Clark AG, et al. APOA5 polymorphisms influence plasma triglycerides in young, healthy AfricanAmericans and whites of the CARDIA Study [J].J Lipid Res, 2005,46(3): 564-571
[44] Nabika T, Nasreen S, Kobayashi S, et al. The genetic effect of the apoprotein AV gene on the serum triglyceride level in Japanese[J]. Athero- sclerosis,2002,165:201-204
[45] Endo K,Yanagi H,Araki J,et al. Association found between the promotereg- ion polymorphism in the apolipoprotein AⅤgene and the serum triglycer- ide level in Japanese schoolchildren [J].Hum Gene,t 2002, 111(6):570-5 72.
[46] Baum L,Tomlinson B,Thomas GN.APOA5-1131T/C polymorphism is associated with triglyceride levels in Chinese men [J]. Clin Genet 2003, 63(5): 377-379.
[47] Li GP,Wang JY,Yan SK, et al. Genetic effect of two polymorphisms in the apolipoprotein A5 gene and apolipoprotein C3 gene on serum lipids and lipoproteins levels in a Chinese population[J].Clin Genet, 2004, 65(6): 470-476
[48] Martin S, Nicaud V, Humphries SE, et al. Contribution of APOA5 gene variants to plasma triglyceride determination and to the response to both fat and glucose tolerance challenges[J]. Biochim Biophys Acta, 2003,1 637: 217-225
[49] Ribalta J,Figuera L,Fernandez-Ballart J,et al.Newly identified apolipopro- tein AV gene predisposes to high plasma triglycerides in familial combinedhyperlipidemia[J].Clin Chem,2002,48:1597-1600
[50] Mar R,Pajukanta P,AllayeeH, et al. Association of the apolipoprotein A1/C3/A4/A5 gene cluster with triglyceride levels and LDL particle size in familial combined hyperlipidemia[J].Circ Res, 2004, 94(7): 993-999.
[51] Aouizerat BE,Kulkarui M,Heilbron D, et al.Genetic analysis of a polymorphism in the human apolipoprotein AV gene, effect or plasma lipids[J].LipidsRes,2003, 44: 1167 -1173.
[52] Austin MA, Talmud PJ, Farin FM, et al. Association of Apolipoprotein A5 variants with LDL particle size and triglyceride in JapaneseAmericans [J]. Biochim Biophys Acta, 2004, 1688(1): 1-9.
[53] Hsu LA, Ko YL, Chang C,h,et al. Genetic variations of apolipoprotein A5 gene is associated with the risk of coronary artery disease Chinese in Taiwan[J]. Atherosclerosis, 2006;143-149.
[54] Liu H,Zhang S, Lin J,et al. Association between DNA variant sites in the apolipoprotein A5 gene and coronary heart disease in Chinese[J]. Metabolism,2005,54 (5):568-572.
[55] Hubacek JA, Skodova Z,Adamkova V, et al. The influence of apoAⅤpolymorphisms (T-1131>C and S19>W) on plasma triglyceride levels and risk of myocardial infarction[J].Clin Genet ,2004, 65(2): 126-130.
[56] Szalai C, Keszei M, Duba J, et al. Polymorphism in the promoter region of the apolipoprotein A5 gene is associated with an increased susceptibility for coronary artery disease [J].Atherosclerosis,2004,173(1): 109-114
[57] Jang Y,Kim JY,Kim OY, et al.The-1131T-->C polymorphism in the apolipoprotein A5 gene is associated with postprandial hypertriacylglycer- olemia;elevated small dense LDL concentration;and oxidative stress in nonobese Koreanmen [J]. AmJ Clin Nutr, 2004, 80(4): 832-840.
[58]Talmud PJ,Martin S,Taskinen MR,et al.APOA5 gene variants, lipoprotein -particle distribution, and progression of coronary heart disease:results from theLOCAT study[J].J Lipid Res,2004,45(4):750-756.
[59] Lai CQ,Demissie S,Cupples LA,et al.Influence of the APOA5 locus on plasma triglyceride,lipoprotein subclasses,and CVD risk in the Framingham HeartStudy [J]. J Lipid Res, 2004, 45(11): 2096-2105.
[60] Lee KW, Ayyobi AF, Frohlich JJ, et al. APOA5 gene polymorphismmo- dulates levels of triglyceride, HDL cholesterol and FERHDL but is not arisk factor for coronary artery disease [J].Atherosclerosis, 2004,176(1): 165-172
[61] Chiu KC,Chiu YF,Boyad-Jian AA.et al.Impact of apolipoprotein A5 polymorphisms on insulin sensitivity and betacell function [J].Pancreas, 2005,30(4):328-332
[62] Yan SK,Cheng XQ,Song YH, et al. Apolipoprotein A5 gene polymorphism -1131T/C: association with plasma lipids and type 2 diabetes mellitus with coronary heart disease in Chinese[J].Clin Chem Lab Med,2005,43(6): 607-612.
[63] Bi N,Yen sk,Li GD,et al. A singhe nucleotole polymorphism -1131T→C in the apolipoprotein A5 gene is associated with increased risk of coronary artery disease and alters triglyceride metabolism in Chinese[J]. Mol Genet Metab,2004,83:280-286.
[64] Esteve E,Faure E,Calvo F, et al.SNP3 polymorphism in apo A-V gene isassociated with small dense LDL particles in TyPe 2 diabetes[J].Diabet- ologia,2004,47:355-356·