中国2型糖尿病患者糖尿病视网膜病变的候选基因关联研究。
Candidate gene association study for diabetic retinopathy in Chinese patients with type 2 diabetes.
作者信息
Yang Xiufen, Deng Yu, Gu Hong, Ren Xuetao, Li Na, Lim Apiradee, Snellingen Torkel, Liu Xipu, Wang Ningli, Liu Ningpu
机构信息
Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing, China ; Department of Ophthalmology, the Friendship Hospital, Capital Medical University, Beijing, China.
Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing, China ; Department of Ophthalmology, Fu Xing Hospital, Capital Medical University, Beijing, China.
出版信息
Mol Vis. 2014 Mar 3;20:200-14. eCollection 2014.
PURPOSE
To investigate whether variants in a set of eight candidate genes are associated with diabetic retinopathy (DR) in a cohort of Chinese patients with type 2 diabetes mellitus (T2DM).
METHODS
Case-control study. Patients with T2DM were recruited from the Desheng community in urban Beijing and assigned into a DR group or diabetic without retinopathy (DWR) group, based on the duration of diabetes and grading of fundus images. Twenty-six single-nucleotide polymorphisms (SNPs) within eight candidate genes, including PPARγ, vascular endothelial growth factor (VEGF) and its receptor kinase insert domain receptor (KDR), erythropoietin, aldose reductase, protein kinase C-β, angiotensin-converting enzyme, and intercellular adhesion molecule 1, were analyzed using the MassARRAY genotyping system.
RESULTS
A total of 500 patients with T2DM (216 with DR and 284 with DWR) were enrolled in the study. Significant associations of DR were noted with genotypes of four SNPs-rs699947 (p<0.001), rs833061 (p = 0.001), rs13207351 (p<0.001), and rs2146323 (p=0.006)--in the VEGF gene and one variant, rs2071559, in the KDR gene (p=0.034). After adjustment for covariates, significant association of DR remained with the homozygous genotype of the minor allele for the SNPs rs699947 (odds ratio [OR] = 3.54, 95% confidence interval [CI]: 1.12-11.19), rs833061 (OR = 3.72, 95% CI: 1.17-11.85), rs13207351 (OR = 3.76, 95% CI: 1.21-11.71), and rs2146323 (OR = 2.8, 95% CI: 1.46-5.37) in the VEGF gene as well as the SNP rs2071559 (OR = 1.62, 95% CI: 1.08-2.41) in the KDR gene. However, only rs699947 and rs13207351 in the VEGF gene remained statistically significant after Bonferroni correction. No associations were found in other genes tested.
CONCLUSIONS
These data expanded previous observations on the association of DR with variants in the VEGF gene in Chinese patients with T2DM. Moreover, a possible association between DR and KDR polymorphisms is suggested.
目的
研究一组8个候选基因的变异是否与中国2型糖尿病（T2DM）患者的糖尿病视网膜病变（DR）相关。
方法
病例对照研究。从北京城区德胜社区招募T2DM患者，根据糖尿病病程和眼底图像分级将其分为DR组或无视网膜病变糖尿病（DWR）组。使用MassARRAY基因分型系统分析8个候选基因（包括PPARγ、血管内皮生长因子（VEGF）及其受体激酶插入结构域受体（KDR）、促红细胞生成素、醛糖还原酶、蛋白激酶C-β、血管紧张素转换酶和细胞间黏附分子1）中的26个单核苷酸多态性（SNP）。
结果
共纳入500例T2DM患者（216例DR患者和284例DWR患者）。发现DR与VEGF基因中的4个SNP（rs699947，p<0.001；rs833061，p = 0.001；rs13207351，p<0.001；rs2146323，p=0.006）以及KDR基因中的1个变异rs2071559（p=0.034）存在显著关联。在对协变量进行校正后，DR与VEGF基因中SNP的次要等位基因纯合基因型仍存在显著关联，rs699947（比值比[OR]=3.54，95%置信区间[CI]：1.12-11.19）、rs833061（OR = 3.72，95% CI：1.17-11.85）、rs13207351（OR = 3.76，95% CI：1.21-11.71）和rs2146323（OR = 2.8，95% CI：1.46-5.37），以及KDR基因中的SNP rs2071559（OR = 1.62，95% CI：1.08-2.41）。然而，经Bonferroni校正后，仅VEGF基因中的rs699947和rs13207351仍具有统计学意义。在其他检测基因中未发现关联。
结论
这些数据扩展了先前关于中国T2DM患者中DR与VEGF基因变异关联的观察结果。此外，提示DR与KDR基因多态性之间可能存在关联。
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