山东泰安地区汉族维生素D受体多态性与终末期肾病及高转运肾性骨病发展关系的研究
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摘要
目的探讨在山东泰安地区汉族中,两种位于维生素D受体(VDR)的基因TaqⅠ(rs731236)和ApaⅠ(rs7975232)的多态性与终末期肾病(ESRD)和肾性骨病进展的关系。方法收集血液透析ESRD患者452例,分别测血甲状旁腺激素(i PTH)、钙、磷、碱性磷酸酶和白蛋白分析。同时,采用PCR-限制性片段长度多态性方法检测VDR基因TaqⅠ和ApaⅠ的多态性。结果 TaqⅠ多态性与ESRD危险性无关。但是杂合子模型(AC/AA:P=0.002;OR=1.4,95%CI 1.14~1.83),纯合子模型CC(CC/AA:P=0.007;OR=1.8,95%CI 1.17~2.85),rs7975232等位基因模型(P<0.001;OR=1.4,95%CI 1.15~1.64)、显性模型(P=0.001;OR=1.5,95%CI 1.19~1.87)和隐性模型(P=0.046;OR=0.6,95%CI 0.42~1.00)均显示ApaⅠ多态性与ESRD风险有关。rs7975232基因型和等位基因频率分布与i PTH水平有关。C等位基因携带者的i PTH水平上升(P=0.005)。结论 VDR基因的ApaⅠ(rs7975232)多态性可能是山东泰安地区汉族ESRD的易感基因,等位基因C携带者发生高转运肾性骨病风险增加。
Objective To replicate the reported association of the two single nucleotide polymorphism(SNP) TaqⅠ(rs731236) and ApaⅠ(rs7975232) above in vitamin D receptor(VDR) gene and end-stage renal disease(ESRD) risk and progression of renal osteodystrophy in Tai'an city. Methods A total of 452 ESRD patients were included in this study. Parathyroid hormone(i PTH), calcium, phosphorus, alkaline phosphatase, and albumin were detected, VDR gene polymorphisms were explored by using PCR fragment length polymorphism method with TaqⅠ and ApaⅠ enzymes in all subjects. Results There were no associations of TaqⅠ(rs731236) polymorphism with ESRD risk. However, there were significant associations of ApaⅠ(rs7975232) polymorphism with ESRD risk, in heterozygote model(AC/AA: P=0.002; OR=1.4, 95% CI 1.14-1.83), homozygote model CC(CC/AA: P=0.007; OR=1.8, 95% CI 1.17-2.85) genotypes for rs7975232, allelic model(P<0.001; OR=1.4, 95% CI 1.15-1.64), dominant model(P=0.001; OR=1.5, 95% CI 1.19-1.87) and recessive model(P=0.046; OR=0.6, 95% CI 0.42-1.00) between cases and healthy controls. Moreover, we found significant correlations of rs7975232 genotypes and allele distributions with i PTH levels. The analysis revealed that allele C carriers might have an increased i PTH level(P=0.005). Conclusion ApaⅠ(rs7975232) polymorphism of VDR gene may be a susceptibility locus for ESRD patients in Tai'an city, Shandong province Han individuals, and allele C carriers have an increased risk of high-turnover renal osteodystrophy.
Objective To replicate the reported association of the two single nucleotide polymorphism(SNP) TaqⅠ(rs731236) and ApaⅠ(rs7975232) above in vitamin D receptor(VDR) gene and end-stage renal disease(ESRD) risk and progression of renal osteodystrophy in Tai'an city. Methods A total of 452 ESRD patients were included in this study. Parathyroid hormone(i PTH), calcium, phosphorus, alkaline phosphatase, and albumin were detected, VDR gene polymorphisms were explored by using PCR fragment length polymorphism method with TaqⅠ and ApaⅠ enzymes in all subjects. Results There were no associations of TaqⅠ(rs731236) polymorphism with ESRD risk. However, there were significant associations of ApaⅠ(rs7975232) polymorphism with ESRD risk, in heterozygote model(AC/AA: P=0.002; OR=1.4, 95% CI 1.14-1.83), homozygote model CC(CC/AA: P=0.007; OR=1.8, 95% CI 1.17-2.85) genotypes for rs7975232, allelic model(P<0.001; OR=1.4, 95% CI 1.15-1.64), dominant model(P=0.001; OR=1.5, 95% CI 1.19-1.87) and recessive model(P=0.046; OR=0.6, 95% CI 0.42-1.00) between cases and healthy controls. Moreover, we found significant correlations of rs7975232 genotypes and allele distributions with i PTH levels. The analysis revealed that allele C carriers might have an increased i PTH level(P=0.005). Conclusion ApaⅠ(rs7975232) polymorphism of VDR gene may be a susceptibility locus for ESRD patients in Tai'an city, Shandong province Han individuals, and allele C carriers have an increased risk of high-turnover renal osteodystrophy.
引文
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[13]Ling Y,Lin H,Aleteng Q,et al.Cdx-2 polymorphism in Vitamin D receptor gene was associated with serum 25-hydroxyvitamin D levels,bone mineral density and fracture in middle-aged and elderly Chinese women[J].Mol Cell Endocrinol,2016,10(16):30062-30064.
[14]阿丽亚,冷兴文,陈瑞英,等.我国维吾尔族妇女维生素D受体基因多态性与骨密度关系的研究[J].解放军保健医学杂志,2002,4(1):41-42.
[15]Garnero P,Sornay-Rendu E,Munoz F,et al.Association of serum sclerostin with bone mineral density,bone turnover,steroid and parathyroid hormones,and fracture risk in postmenopausal women:the OFELY study[J].Osteoporos Int,2013,24(2):489-394.
[16]Jorgensen HL,Scholler J,Sand JC,et al.Relation of comm on allelic variation at vitamin D receptor locus to bone mineral density and postmenopausal bone loss:cross-section and longitudinal population study[J].BMJ,1996,313(7057):586-890.
[17]Gong G,Stern HS,Cheng SC,et al.The association of bone mineral density with vitamin D receptor gene polymorphisms[J].Osteoporos Int,1999,9(1):55-64.
[18]Yokoyama K,Shigematsu T,Tsukada T,et al.ApaⅠpolymorphism in the vitamin D receptor gene may affect the parathyroid response in Japanese with end-stage renal disease[J].Kidney Int,1998,53(2):454-458.
[2]Narooie-Nejad M,Moossavi M,Torkamanzehi A,et al.Positive association of vitamin D receptor gene variations with multiple sclerosis in South East Iranian population[J].Biomed Res Int,2015,20(1):427519.
[3]Zhou TB,Jiang ZP,Huang MF.Association of vitamin D receptor BsmⅠ(rs1544410)gene polymorphism with the chronic kidney disease susceptibility[J].J Recept Signal Transduct Res,2015,35(1):54-57.
[4]Zhou TB,Jiang ZP,Huang MF,et al.Association of vitamin D receptor Fok1(rs2228570),TaqⅠ(rs731236)and ApaⅠ(rs7975232)gene polymorphism with the risk of chronic kidney disease[J].J Recept Signal Transduct Res,2015,35(1):58-62.
[5]Pourfarzam,Nia KM,Atapour A,et al.The influence of BsmⅠand TaqⅠvitamin D receptor gene polymorphisms on the intensity of hyperparathyroidism in Iranian hemodialysis patients[J].Adv Biomed Res,2014,20(3):213.
[6]Singh M,Singh P,Singh S,et al.Vitamin D receptor(VDR)gene polymorphism influences the risk of osteoporosis in postmenopausal women of Northwest India[J].Arch Osteoporos,2013,22(8):147.
[7]Marozik P,Mosse I,Alekna V,et al.Association Between Polymorphisms of VDR,COL1A1,and LCT genes and bone mineral density in Belarusian women with severe postmenopausal osteoporosis[J].Medicina(Kaunas),2013,49(4):177-184.
[8]Conti V,Russomanno G,Corbi G,et al.A polymorphism at the translation start site of the vitamin D receptor gene is associated with the response to anti-osteoporotic therapy in postmenopausal women from southern Italy[J].Int J Mol Sci,2015,16(3):5452-5466.
[9]Jiménez-Salas Z,Hernández-Tobías EA,Ramírez-López TE,et al.Association of polymorphism TaqⅠof vitamin de receptor with bone mineral density in young Mexican women[J].Nutr Hosp,2012,27(5):1505-1510.
[10]Laaksonen MM,Outila TA,Karkkainen MU,et al.Associations of vitamin D receptor,calcium-sensing receptor and parathyroid hormone gene polymorphisms with calcium homeostasis and peripheral bone density in adult Finns[J].J Nutrigenet Nutrigenomics,2009,2(2):55-63.
[11]Arabi A,Mahfoud Z,Zahed L,et al.Effect of age,gender and calciotropic hormones on the relationship between vitamin D receptorgene polymorphisms and bone mineral density[J].Eur J Clin Nutr,2010,64(4):383-391.
[12]Pouresmaeili F,Jamshidi J,Azargashb E,et al.Association between Vitamin D Receptor Gene BsmⅠPolymorphism and Bone Mineral Density in A Population of 146 Iranian Women[J].Cell J,2013,15(1):75-82.
[13]Ling Y,Lin H,Aleteng Q,et al.Cdx-2 polymorphism in Vitamin D receptor gene was associated with serum 25-hydroxyvitamin D levels,bone mineral density and fracture in middle-aged and elderly Chinese women[J].Mol Cell Endocrinol,2016,10(16):30062-30064.
[14]阿丽亚,冷兴文,陈瑞英,等.我国维吾尔族妇女维生素D受体基因多态性与骨密度关系的研究[J].解放军保健医学杂志,2002,4(1):41-42.
[15]Garnero P,Sornay-Rendu E,Munoz F,et al.Association of serum sclerostin with bone mineral density,bone turnover,steroid and parathyroid hormones,and fracture risk in postmenopausal women:the OFELY study[J].Osteoporos Int,2013,24(2):489-394.
[16]Jorgensen HL,Scholler J,Sand JC,et al.Relation of comm on allelic variation at vitamin D receptor locus to bone mineral density and postmenopausal bone loss:cross-section and longitudinal population study[J].BMJ,1996,313(7057):586-890.
[17]Gong G,Stern HS,Cheng SC,et al.The association of bone mineral density with vitamin D receptor gene polymorphisms[J].Osteoporos Int,1999,9(1):55-64.
[18]Yokoyama K,Shigematsu T,Tsukada T,et al.ApaⅠpolymorphism in the vitamin D receptor gene may affect the parathyroid response in Japanese with end-stage renal disease[J].Kidney Int,1998,53(2):454-458.