A genome-wide association study for diabetic nephropathy genes in African Americans.
A genome-wide association study for diabetic nephropathy genes in African Americans.
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DOI：
10.1038/ki.2010.467
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发表时间：
2011-03
影响因子：
19.6
通讯作者：
Bowden DW
中科院分区：
文献类型：
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作者：
McDonough CW;Palmer ND;Hicks PJ;Roh BH;An SS;Cooke JN;Hester JM;Wing MR;Bostrom MA;Rudock ME;Lewis JP;Talbert ME;Blevins RA;Lu L;Ng MC;Sale MM;Divers J;Langefeld CD;Freedman BI;Bowden DW
使用Affytron 6.0芯片进行全基因组关联研究，以确定与非裔美国人糖尿病肾病相关的基因。对965例伴有终末期肾病（ESRD）的2型糖尿病非裔美国人患者和1029例无2型糖尿病或肾病的非裔美国人进行了调整混合物的相关性分析。然后在另外709例2型糖尿病-ESRD患者和690例对照的重复样本中对与糖尿病肾病相关的前724个单核苷酸多态性（SNP）进行基因分型。在原始研究和重复研究中有关联证据的SNP在由1246名无肾脏疾病的2型糖尿病患者和1216名非糖尿病ESRD患者组成的额外的非洲裔美国人队列中进行了测试，以区分2型糖尿病ESRD、2型糖尿病和/或全因ESRD的候选基因座。25个SNPs在全基因组关联和初始复制中与2型糖尿病-ESRD显著相关。虽然这25个SNP中的任何一个都没有发现2型糖尿病的全基因组意义，但包括RPS 12，LIMK 2和SFI 1在内的几个基因是糖尿病肾病的强有力候选者。对所有2890例ESRD患者的联合分析显示LIMK 2和SFI 1中的SNP具有显著关联，表明它们也有助于全因ESRD。因此，我们的研究结果表明，多个基因座是非裔美国人2型糖尿病肾病易感性的基础，有些基因座也可能导致全因终末期肾病。
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.