Evaluation of a SNP map of 6q24-27 confirms diabetic nephropathy loci and identifies novel associations in type 2 diabetes patients with nephropathy from an African-American population.
Evaluation of a SNP map of 6q24-27 confirms diabetic nephropathy loci and identifies novel associations in type 2 diabetes patients with nephropathy from an African-American population.
复制标题
对 6q24-27 SNP 图谱的评估证实了糖尿病肾病位点，并确定了 2 型糖尿病患者与非裔美国人肾病之间的新关联。
DOI：
10.1007/s00439-008-0523-7
复制
发表时间：
2008
期刊：
影响因子：
5.3
通讯作者：
Sale,MichèleM
中科院分区：
文献类型：
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作者：
Leak,TennilleS;Mychaleckyj,JosyfC;Smith,ShellyG;Keene,KeithL;Gordon,CandaceJ;Hicks,PamelaJ;Freedman,BarryI;Bowden,DonaldW;Sale,MichèleM
此前，我们对来自247个家庭的638对受非裔美国人(AA)影响的同胞对进行了2型糖尿病(T2 DM)的基因组扫描；非参数连锁分析表明有证据表明6q24-27(LOD 2.26)存在连锁。为了全面评估该区域，我们进行了一项两阶段关联研究，首先在300名AAT2 DM终末期肾病(ESRD)受试者、311名AA对照、43名欧美对照和45名约鲁巴尼日利亚样本(SET 1)中，根据连锁不平衡(LD)构建了从HapMap中选择的754个SNP的SNP图谱。在283名2型糖尿病-终末期肾病患者和282名AA对照组(第2组)的独立人群中进行了复制分析。此外，我们使用祖先信息标记(AIMS)调整了混合因素对关联结果的影响。在第一阶段，137个(18.2%)SNPs在一个或多个关联性检验中显示出名义上的关联证据(P<；N0.05)：等位基因(n=333)、显性(n=336)、加性(n=229)或隐性(n=334)基因模型，以及2-(n=947)和3-SNP(n=843)单倍型分析。选择这些SNPs进行后续基因分型。阶段2分析证实与预测的PARK2基因中的2-SNP单倍型有关。两个基因间SNPs与T2 DM-ESRD有一致的关联：rs12197043和rs4897081。对来自两个阶段的所有受试者的联合分析显示，名义上与基因内的17个SNP有关，包括ESR1和PARK2中的暗示关联。这项研究证实了已知的糖尿病肾病基因座，并发现了位于AA中6q24-27的潜在新的易感变异。
Previously, we performed a genome scan for type 2 diabetes (T2DM) using 638 African-American (AA) affected sibling pairs from 247 families; non-parametric linkage analysis suggested evidence of linkage at 6q24–27 (LOD 2.26). To comprehensively evaluate this region, we performed a two-stage association study by first constructing a SNP map of 754 SNPs selected from HapMap on the basis of linkage disequilibrium (LD) in 300 AAT2DM end-stage renal disease (ESRD) subjects, 311 AA controls, 43 European American controls and 45 Yoruba Nigerian samples (Set 1). Replication analyses were conducted in an independent population of 283 AA T2DM-ESRD subjects and 282 AA controls (Set 2). In addition, we adjusted for the impact of admixture on association results by using ancestry informative markers (AIMs). In Stage 1, 137 (18.2%) SNPs showed nominal evidence of association (P< 0.05) in one or more of tests of association: allelic (n= 33), dominant (n= 36), additive (n= 29), or recessive (n= 34) genotypic models, and 2- (n= 47) and 3-SNP (n= 43) haplotypic analyses. These SNPs were selected for follow-up genotyping. Stage 2 analyses confirmed association with a predicted 2-SNP “risk” haplotype in thePARK2gene. Also, two intergenic SNPs showed consistent genotypic association with T2DM-ESRD: rs12197043 and rs4897081. Combined analysis of all subjects from both stages revealed nominal associations with 17 SNPs within genes, including suggestive associations inESR1andPARK2.This study confirms known diabetic nephropathy loci and identifies potentially novel susceptibility variants located within 6q24–27 in AA.