摘要背景 晚期糖基化终末产物特异性受体(RAGE)在2型糖尿病及其微血管并发症的发病过程中发挥重要作用.RAGE基因Gly82Ser存在多态性,但其与糖尿病视网膜病变(DR)的相关性有待进一步研究. 目的 探讨无锡地区汉族人群RAGE基因Gly82Ser多态性与DR的关系. 方法 采用横断面研究方法,于2013年3月至2014年2月在无锡纳入汉族无亲缘关系的2型糖尿病患者185例,依据2002年DR国际临床分型标准将患者分为非DR(NDR)组(93例)和DR组(92例),同期纳入健康体检对照者120名.各位受检者均行眼部检查、血液生物化学指标及血脂等实验室检查和血压、体质量指数(BMI)及空腹血糖水平检测.采集受检者外周血各3 ml,采用PCR-直接测序法检测受检者的基因型及等位基因频率并进行组间差异比较.结果 DR组患者糖尿病病程明显长于NDR组,差异有统计学意义(t=2.25,P=0.01).DR组、NDR组及健康对照组受检者RAGE基因Gly82Ser位点均存在G和A2种等位基因,其多态性分布符合Hardy-Weinberg遗传平衡定律(DR组:x2=0.51,P=0.48;NDR组:x2=1.38,P=0.24;健康对照组:x2=0.20,P=0.24).DR组、NDR组患者和健康对照组受检者AA基因型频率分别为6.5％、3.2％和2.5％,DR组患者AA基因型频率高于NDR组及健康对照组,差异均有统计学意义(x2=5.146,P=0.023;x2=5.039,P=0.037);DR组受检者A等位基因频率分布明显高于NDR组及健康对照组,差异均有统计学意义(x2=5.494,P=0.019;x2=5.235,P=0.023),而GG基因型及G等位基因频率低于NDR组和健康对照组,差异均有统计学意义(GG:x2=4.260,P=0.039x2 =4.794,P=0.027;G:x2 =5.309,P=0.021;x2=5.476,P=0.032);NDR组与健康对照组间受检者各基因型及等位基因频率的差异均无统计学意义(AA:x2=5.346,P=0.127;GG:x2 =6.981,P=0.137;A;x2=5.618,P=0.082;G:x2=4.860,P=0.088). 结论 RAGE基因Gly82Ser位点单核苷酸多态性与无锡地区2型糖尿病患者DR的发生有一定的关联,A等位基因可能是促进其发病的危险因素.

abstractsBackground Receptor for advanced glycation end products (RAGE) play an important role in the process of type 2 diabetes and its microvascular complications.RAGE gene Gly82Ser exists polymorphism,but the correlation of gene polymorphism and diabetic retinopathy (DR) needs further research.Objective This study was to investigate the association of Gly82Ser polymorphism of RAGE gene with DR in Han people of Wuxi area with type 2 diabetic mellitus.Methods One hundred and eighty-five patiens with type 2 diabetes were included in Wuxi district from March 2013 to February 2014.The patients were divided into non DR (NDR) group (93 cases) and DR group (92 cases) according to the DR International Clinical Classification Criteria in 2002,and 120 healthy subjects were included at the same time as the control.All of the subjects received eye examinations,body mass index (BMI) and blood pressure measurement as well as laboratory tests,including blood biochemical indexes,blood lipids and fasting blood glucose levels.The peripheral blood of 3 ml was collected from each subject,and the genotype and allelic frequencies were assayed by PCR-direct sequencing.This study protocol was approved by Ethic Committee of Nanjing Medical University.Written informed consent was obtained from each subject prior to any medical examination.Results The course was significantly longer in the DR group than that in the NDR group (t =2.25,P =0.01).There were two alleles of G and A in the RAGE gene Gly82Ser locus in all the subjects and the distribution of single nucleotide polymorphism was in accordance with Hardy-Weinberg equilibrium (DR group:x2 =0.51,P =0.48;NDR group:x2 =1.38,P =0.24;healthy control group:x2 =0.20,P =0.24).The AA genotype frequency of the subjects in DR group,NDR group and healthy control group were respectively 6.5％,3.2％ and 2.5％,and AA genotype frequency in DR group was higher than that of the NDR group and healthy control group,showing significant intergroup differences (x2 =5.146,P =0.023;x2 =5.039,P =0.037).The distribution of A allele frequency in the DR group was significantly higher than that of NDR group and healthy control group (x2=5.494,P=0.019;x2 =5.235,P =0.023),and the frequencies of G allele and GG genotype in the DR group were lower than those of the NDR and the healthy control group (GG:x2 =4.260,P =0.039;x2 =4.794,P =0.027;G:x2 =5.309,P =0.021;x2 =5.476,P=0.032).No significant differences were seen in the frequencies of genotype and allele of subjects between the NDR group and the healthy control group (AA:x2 =5.346,P=0.127;GG:x2 =6.981,P=0.137;A:x2 =5.618,P =0.082;G:x2 =4.860,P =0.088).Conclusions The Gly82Ser polymorphism of RAGE gene is associated with the pathogenesis of DR in Han population with type 2 diabetes and A allele may be a risk factor of DR.