[内皮型一氧化氮合酶基因串联重复序列多态性数量可变与糖尿病视网膜病变的关联]

[The association of variable number of tandem repeats polymorphism in the endothelial nitric oxide synthase gene and diabetic retinopathy].

作者信息

She Chongyang, Yang Xiufen, Gu Hong, Deng Yu, Xu Jun, Ma Kai, Liu Ningpu

机构信息

Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing 100730, China.

Email:

出版信息

Zhonghua Yan Ke Za Zhi. 2015 May;51(5):338-43.

PMID:26311693

Abstract

OBJECTIVE

To investigate the association between the variable number of tandem repeats (VNTR) polymorphism 4a/b in the endothelial nitric oxide synthase (eNOS) gene and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus.

METHODS

cross-sectional study. A total of 278 type 2 diabetes patients were recruited, of whom 130 had DR, and 148 had diabetes without retinopathy (DWR). Of the 130 patients with DR, 34 had proliferative DR (PDR) and 96 had non-proliferative DR (NPDR). A number of 223 volunteers without diabetes from the same area were recruited as the control group. PCR and agarose gel electrophoresis methods were adopted to determine the 4a/b polymorphism genotypes of the eNOS gene. Statistical analysis was performed using the R statistical analysis package. Genotype distribution was compared using the χ(2) test. Numerical data were examined by Student t test. Genotypes and allele frequencies between cases and controls were compared using the χ(2) test or Fisher's exact test. Odd ratios (OR) and 95% confidence intervals (CI) were calculated according to the Woolf's equation.

RESULTS

The frequencies of minor alleles (a) were 10.8% and 11.5% in the DR and DWR group, respectively. There were no statistical differences between the two groups (χ(2) = 0.07, P = 0.789). Also there were no statistical differences (χ(2) = 0.88; P = 0.643) in the distributions of the genotypes between DR group (bb 78.5%, ab 21.5%, aa 0.0%) and DWR group (bb 77.7%, ab 21.6%, aa 0.7%). Statistical differences were found in the frequencies of alleles, and the distributions of genotypes between diabetes group and the control group (χ(2) = 8.75, 10.39, P = 0.003, 0.006). However, after adjustment for age, blood pressure, cholesterol concentration, blood-fat and so on, it became insignificant (χ(2) = 0.97, 1.25, P = 3.224, 0.812). In the multiple regressions model including clinic factors such as the age of onset of diabetes, urinary albumin, insulin using, creatinine, glycated hemoglobin and fast glucose, no evidence showed that eNOS gene VNTR 4a/b was associated with diabetic retinopathy (OR = 0.37, 95% CI: 0.15-0.95).

CONCLUSION

There was no significant association between eNOS gene VNTR 4a/b polymorphism and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus.

摘要

目的

探讨内皮型一氧化氮合酶（eNOS）基因可变数目串联重复序列（VNTR）4a/b多态性与2型糖尿病患者糖尿病视网膜病变（DR）之间的关联。

方法

横断面研究。共纳入278例2型糖尿病患者，其中130例患有DR，148例患有糖尿病但无视网膜病变（DWR）。在130例DR患者中，34例为增殖性DR（PDR），96例为非增殖性DR（NPDR）。招募了来自同一地区的223名无糖尿病志愿者作为对照组。采用聚合酶链反应（PCR）和琼脂糖凝胶电泳方法确定eNOS基因的4a/b多态性基因型。使用R统计分析软件包进行统计分析。采用χ²检验比较基因型分布。数值数据采用学生t检验。采用χ²检验或Fisher精确检验比较病例组和对照组之间的基因型和等位基因频率。根据Woolf方程计算比值比（OR）和95%置信区间（CI）。

结果

DR组和DWR组的次要等位基因（a）频率分别为10.8%和11.5%。两组之间无统计学差异（χ² = 0.07，P = 0.789）。DR组（bb 78.5%，ab 21.5%，aa 0.0%）和DWR组（bb 77.7%，ab 21.6%，aa 0.7%）之间的基因型分布也无统计学差异（χ² = 0.88；P = 0.643）。糖尿病组与对照组之间的等位基因频率和基因型分布存在统计学差异（χ² = 8.75，10.39，P = 0.003，0.006）。然而，在调整年龄、血压、胆固醇浓度、血脂等因素后，差异变得不显著（χ² = 0.97，1.25，P = 3.224，0.812）。在包括糖尿病发病年龄、尿白蛋白、胰岛素使用、肌酐、糖化血红蛋白和空腹血糖等临床因素的多元回归模型中，没有证据表明eNOS基因VNTR 4a/b与糖尿病视网膜病变相关（OR = 0.37，95% CI：0.15 - 0.95）。