内皮型一氧化氮合酶基因内含子的数目可变串联重复多态性与糖尿病视网膜病变的相关性研究  

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

作　　者：余重阳 杨秀芬[2] 顾虹[1] 邓禹[3] 徐军[1] 马凯[1] 刘宁朴[1] 

机构地区：[1]首都医科大学附属北京同仁医院北京同仁眼科中心北京市眼科学与视觉科学重点实验室,100730 [2]首都医科大学附属北京友谊医院 [3]首都医科大学附属复兴医院眼科

出　　处：《中华眼科杂志》2015年第5期338-343,共6页Chinese Journal of Ophthalmology

摘　　要：目的探讨内皮型一氧化氮合酶（eNOS）基因内含子的数目可变串连重复多态性（VNTR）4a／b与糖尿病视网膜病变（DR）的相关性。方法横断面研究。收集北京市德外社区2型糖尿病患者278例，其中DR组130例，无视网膜病变（DwR）组148例；DR组中增殖性DR（PDR）34例，非增殖性DR（NPDR）96例；收集同一地区非糖尿病志愿者223例作为同源非糖尿病对照人群。采用PCR和琼脂糖凝胶电泳技术检测eNOS基因的VNTR4a／b基因型。采用R统计软件进行数据分析。采用卡方检验验证基因型分布是否符合Hardy．Weinberg平衡定律。组间年龄比较采用Studentt检验，性别比例、基因型和等位基因出现频率比较采用卡方检验或Fisher精确概率检验，比值比和95％可信区间根据Woolf等式计算。结果eNOS基因VNTR4a／b多态性的低频率等位基因a在DR组和DWR组频率分别为10．8％和11．5％，两组相比差异无统计学意义（x2=0．07，P=0．789）。4a／b基因型分布DR组（bb78．5％，ab21．5％，aa0．0％）与DWR组（bh77．7％，ab21．6％，aa0．7％）相比差异亦无统计学意义（x2=0．88，P=0．643）。该多态性的等位基因及基因型频率在糖尿病组与非糖尿病组之间的差异存在统计学意义（x2=8．75，10．39；P=0．003，0．006），但是在进行年龄、空腹血糖、胆固醇、血脂等因素校正后无意义（x2=0．97，1．25；P=3．224，0．812）。在多因素回归分析模型中，纳入患者入组年龄、尿微量白蛋白定量、胰岛素使用、肌酐、糖化血红蛋白及血糖等变量后，VNTR4a／b多态性与DR发病仍无相关性（0R=0．37，95％可信区间：0．15～0．95）。结论eNOS基因内含子重复序列4a／b多态性与2型糖尿病人群DR的发病无明显相关性。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 X2 test. Numerical data were examined by Student t test.Genotypes and allele frequencies between cases and controls were compared using the X2 test or Fisher＇s exact test. Odd ratios （OR） and 95% confidence intervals （C/） 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 （X2=0.07, P=0.789）. Also there were no statistical differences （X2=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 （X==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（x2=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

关 键 词：糖尿病视网膜病变 一氧化氮合酶Ⅲ型 内含子 小卫星重复 多态现象 遗传 

分 类 号：R587.2[医药卫生—内分泌]