Variants in the gene encoding aldose reductase (AKR1B1) and diabetic nephropathy in American Indians
Variants in the gene encoding aldose reductase (AKR1B1) and diabetic nephropathy in American Indians
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DOI：
10.1111/j.1464-5491.2006.01834.x
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发表时间：
2006-04-01
影响因子：
3.5
通讯作者：
Hanson, RL
中科院分区：
文献类型：
--
作者：
Wolford, JK;Yeatts, KA;Hanson, RL
醛糖还原酶基因（AKR 1B 1）是糖尿病肾病的一个强有力的候选基因，rs759853的T等位基因和[AC]（n）微卫星的Z-2等位基因在某些人群中与糖尿病肾病相关。由于AKR 1B 1位于7 q35，我们以前曾报道过在皮马印第安人糖尿病肾病的联系，本研究探讨了AKR 1B 1变异与糖尿病肾病在这个population.Methods的关联AKR 1B 1变异体通过测序和基因分型使用等位基因歧视和焦磷酸测序。比较107例糖尿病终末期肾病患者和108例糖尿病对照者的基因型分布。结果在141例肾病患者和416例无严重蛋白尿患者中，共发现11个AKR 1B 1单核苷酸多态性（SNP）和[AC]（n）微卫星多态性。三个SNP是罕见的，两个是在100%的基因型一致性，因此，8个多态性基因分型。在病例对照或以家族为基础的研究中，没有变异与糖尿病肾病相关。例如，rs759853处的T等位基因在病例中的等位基因频率为0.165，在对照受试者中的等位基因频率为0.171（OR = 0.96，95% CI为0.57-1.59，P = 0.86）;在家系调查中，患病者和未患病者的频率分别为0.140和0.169（OR = 0.90，95% CI，0.53-1.54 P = 0.71）。在[AC]（n）微卫星上Z-2等位基因的相应值为OR = 1.09（95% CI 0.72-1.66，P = 0.67）和OR = 1.25（95% CI 0.81-1.95，P = 0.31），结论AKR 1B 1基因多态性可能不是糖尿病肾病的主要决定因素。
Aims The aldose reductase gene (AKR1B1) is a strong candidate for diabetic nephropathy, and the T allele at rs759853 and the Z-2 allele at an [AC](n) microsatellite are associated with diabetic kidney disease in some populations. As AKR1B1 is located on 7q35, where we have previously reported linkage to diabetic nephropathy in Pima Indians, this study examined the association of AKR1B1 variants with diabetic nephropathy in this population.Methods AKR1B1 variants were identified by sequencing and genotyped using allelic discrimination and pyrosequencing. Genotype distributions were compared between 107 cases with diabetic end-stage renal disease and 108 control subjects with diabetes for ! 10 years and no evidence of nephropathy, and between 141 individuals with nephropathy and 416 individuals without heavy proteinuria in a family study of 257 sibships.Results We identified 11 AKR1B1 single nucleotide polymorphisms (SNPs) and the [AC](n) microsatellite polymorphism. Three SNPs were rare and two were in 100% genotypic concordance; thus, eight polymorphisms were genotyped. No variant was associated with diabetic kidney disease in the case-control or family-based study. For example, the T allele at rs759853 had ail allele frequency of 0.165 in cases and 0.171 in control subjects (OR = 0.96, 95% CI, 0.57-1.59, P = 0.86); in the family study its frequency was 0.140 and 0.169 in affected and unaffected individuals, respectively (OR = 0.90, 95% CI, 0.53-1.54 P = 0.71). Corresponding values for the Z-2 allele at the [AC](n) microsatellite were OR = 1.09 (95% CI 0.72-1.66, P = 0.67) and OR = 1.25 (95% CI 0.81-1.95, P = 0.31) in the case-control and family studies, respectively.Conclusions Common AKR1B1 polymorphisms are unlikely to be major determinants of diabetic nephropathy in this population.