McKnight Amy Jayne, Maxwell Alexander P, Fogarty Damian G, Sadlier Denise, Savage David A
Nephrology Research Group, Queen's University of Belfast, Belfast, Northern Ireland.
Nephrol Dial Transplant. 2009 Aug;24(8):2473-6. doi: 10.1093/ndt/gfp015. Epub 2009 Mar 31.
Diabetic nephropathy is a leading cause of end-stage renal disease. Premature mortality is common in patients with nephropathy, largely due to cardiovascular disease. Genetic variants implicated in macrovascular disease are therefore excellent candidates to assess for association with diabetic nephropathy. Recent genome-wide association studies have identified a total of 15 single-nucleotide polymorphisms (SNPs) that are reproducibly associated with cardiovascular disease.
We initially assessed these SNPs for association in UK type 1 diabetic patients with (cases; n = 597) and without (controls; n = 502) nephropathy using iPLEX(TM) and TaqMan(R) assays. Replication studies were performed with DNA genotyped in a total of 2668 individuals from the British Isles.
One SNP (rs4420638) on chromosome 19q13 was found to be significantly associated with diabetic nephropathy before (P = 0.0002) and after correction for multiple testing (P(corrected) = 0.002). We replicated this finding in a phenotypically similar case-control collection comprising 709 individuals with type 1 diabetes (P = 0.002; combined P < 0.00001; OR = 1.54, 95% CI: 1.29-1.84).
Our case-control data suggest that rs4420638, or a functional SNP in linkage disequilibrium with this SNP, may be associated with diabetic nephropathy.
糖尿病肾病是终末期肾病的主要病因。肾病患者过早死亡很常见，主要是由于心血管疾病。因此，与大血管疾病相关的基因变异是评估与糖尿病肾病关联的极佳候选因素。最近的全基因组关联研究共鉴定出15个与心血管疾病可重复关联的单核苷酸多态性（SNP）。
我们最初使用iPLEX™和TaqMan®检测法评估这些SNP在患有（病例组；n = 597）和未患有（对照组；n = 502）肾病的英国1型糖尿病患者中的关联性。在来自不列颠群岛的总共2668名个体中对DNA进行基因分型，进行重复研究。
发现位于19号染色体q13上的一个SNP（rs4420638）在多重检验校正之前（P = 0.0002）和之后（校正后P = 0.002）均与糖尿病肾病显著相关。我们在一个包含709名1型糖尿病患者的表型相似的病例对照样本中重复了这一发现（P = 0.002；合并P < 0.00001；OR = 1.54，95% CI：1.29 - 1.84）。
我们的病例对照数据表明，rs4420638或与该SNP处于连锁不平衡状态的一个功能性SNP可能与糖尿病肾病相关。
