CPVL/CHN2 genetic variant is associated with diabetic retinopathy in Chinese type 2 diabetic patients.
CPVL/CHN2 genetic variant is associated with diabetic retinopathy in Chinese type 2 diabetic patients.
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作者：
Hu C;Zhang R;Yu W;Wang J;Wang C;Pang C;Ma X;Bao Y;Xiang K;Jia W
糖尿病肾病和视网膜病变是糖尿病的两个重要微血管并发症，在糖尿病患者中具有很高的一致率。最近在欧洲血统的1型糖尿病患者中进行的全基因组关联研究确定了与糖尿病肾病相关的四个位点。本研究的目的是检测这四个位点的单核苷酸多态性（SNPs）与中国2型糖尿病患者糖尿病肾病和视网膜病变的关系。在第1阶段，我们招募了1,276名2型糖尿病患者，包括378名糖尿病肾病但无视网膜病变的患者，374名糖尿病视网膜病变但无肾病的患者，244名糖尿病视网膜病变和肾病患者，以及280名糖尿病>10年且无糖尿病视网膜病变或肾病的对照受试者。对来自4个位点（CPVL/CHN 2、FRMD 3、汽车和IRS 2）的55个SNP进行基因分型。显示与糖尿病视网膜病变或肾病相关的SNP在第2阶段样品中进行基因分型以用于复制。来自CPVL/CHN 2和FRMD 3的SNP与糖尿病视网膜病变相关，其中rs39059和rs 10868025是最高的SNP（比值比[OR] 1.292，95% CI 1.097-1.523，P = 0.0022，rs39059; 1.201，1.014-1.422，P = 0.0343，rs 10868025）。在第2阶段分析中，只有rs39059显示与糖尿病视网膜病变相似的效果（OR 1.269，0.989-1.628，P = 0.0689），荟萃分析显示rs39059与糖尿病视网膜病变显著相关，OR为1.285（1.120-1.474，P = 0.0003）。CPVL/CHN 2 rs39059也与糖尿病视网膜病变水平相关（趋势P = 0.0007）。然而，这些SNPs与糖尿病肾病之间没有相关性。在本研究中，我们发现CPVL/CHN 2 rs39059与中国2型糖尿病患者的糖尿病视网膜病变相关。
Diabetic nephropathy and retinopathy are two important microvascular diabetes complications with a high concordance rate in diabetic patients. A recent genome-wide association study in type 1 diabetic patients of European descent identified four loci to be associated with diabetic nephropathy. The aim of this study was to test the effects of single nucleotide polymorphisms (SNPs) from these four loci on diabetic nephropathy and retinopathy in Chinese type 2 diabetic patients. In stage 1, we recruited 1,276 type 2 diabetic patients, including 378 patients with diabetic nephropathy but no retinopathy, 374 patients with diabetic retinopathy but no nephropathy, 244 patients with both diabetic retinopathy and nephropathy, and 280 control subjects with diabetes for >10 years and no diabetic retinopathy or nephropathy. Fifty-five SNPs from four loci (CPVL/CHN2, FRMD3, CARS, and IRS2) were genotyped. The SNPs that showed associations to diabetic retinopathy or nephropathy were genotyped in stage 2 samples for replication. SNPs from CPVL/CHN2 and FRMD3 were associated with diabetic retinopathy with rs39059 and rs10868025 as the top SNPs (odds ratio [OR] 1.292, 95% CI 1.097–1.523, P = 0.0022, for rs39059; 1.201, 1.014–1.422, P = 0.0343, for rs10868025) in stage 1 samples. In stage 2 analysis, only rs39059 showed similar effect to diabetic retinopathy (OR 1.269, 0.989–1.628, P = 0.0689), and meta-analysis showed a significant association between rs39059 and diabetic retinopathy, with an OR of 1.285 (1.120–1.474, P = 0.0003). CPVL/CHN2 rs39059 was also associated with levels of diabetic retinopathy (P = 0.0007 for trend). However, no association was detected between these SNPs and diabetic nephropathy. In this study, we found CPVL/CHN2 rs39059 was associated with diabetic retinopathy in the Chinese type 2 diabetic patients.
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