Program in Molecular Medicine and Translational Science, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Kidney Int. 2011 Mar;79(5):563-72. doi: 10.1038/ki.2010.467. Epub 2010 Dec 8.
A genome-wide association study was performed using the Affymetrix 6.0 chip to identify genes associated with diabetic nephropathy in African Americans. Association analysis was performed adjusting for admixture in 965 type 2 diabetic African American patients with end-stage renal disease (ESRD) and in 1029 African Americans without type 2 diabetes or kidney disease as controls. The top 724 single nucleotide polymorphisms (SNPs) with evidence of association to diabetic nephropathy were then genotyped in a replication sample of an additional 709 type 2 diabetes-ESRD patients and 690 controls. SNPs with evidence of association in both the original and replication studies were tested in additional African American cohorts consisting of 1246 patients with type 2 diabetes without kidney disease and 1216 with non-diabetic ESRD to differentiate candidate loci for type 2 diabetes-ESRD, type 2 diabetes, and/or all-cause ESRD. Twenty-five SNPs were significantly associated with type 2 diabetes-ESRD in the genome-wide association and initial replication. Although genome-wide significance with type 2 diabetes was not found for any of these 25 SNPs, several genes, including RPS12, LIMK2, and SFI1 are strong candidates for diabetic nephropathy. A combined analysis of all 2890 patients with ESRD showed significant association SNPs in LIMK2 and SFI1 suggesting that they also contribute to all-cause ESRD. Thus, our results suggest that multiple loci underlie susceptibility to kidney disease in African Americans with type 2 diabetes and some may also contribute to all-cause ESRD.
一项全基因组关联研究使用 Affymetrix 6.0 芯片进行，旨在鉴定与非洲裔美国人糖尿病肾病相关的基因。在 965 名患有终末期肾病（ESRD）的 2 型糖尿病非洲裔美国患者和 1029 名无 2 型糖尿病或肾脏疾病的非洲裔美国人中，通过调整混合因素进行关联分析。在另外 709 名 2 型糖尿病 ESRD 患者和 690 名对照的复制样本中，对与糖尿病肾病有明显关联的前 724 个单核苷酸多态性（SNP）进行了基因分型。在原始和复制研究中均有明显关联的 SNP 在另外两个由 1246 名无肾脏疾病的 2 型糖尿病患者和 1216 名非糖尿病 ESRD 患者组成的非洲裔美国人队列中进行了检测，以区分候选基因与 2 型糖尿病 ESRD、2 型糖尿病和/或所有原因 ESRD。在全基因组关联和初步复制中，有 25 个 SNP 与 2 型糖尿病 ESRD 显著相关。尽管这些 25 个 SNP 中没有任何一个与 2 型糖尿病具有全基因组意义，但包括 RPS12、LIMK2 和 SFI1 在内的几个基因是糖尿病肾病的有力候选基因。对所有 2890 名 ESRD 患者的综合分析显示，在 LIMK2 和 SFI1 中存在显著关联的 SNP，这表明它们也与所有原因的 ESRD 有关。因此，我们的研究结果表明，多个基因座是导致非洲裔美国人 2 型糖尿病患者易患肾脏疾病的原因，其中一些基因座也可能导致所有原因的 ESRD。
