血管内皮生长因子3’非翻译区936C/T突变与糖尿病视网膜病变的关系  

Relationship between 936C/T polymorphism in 3'-untranslated region of vascular endothelial growth factor gene and diabetic retinopathy in China

作　　者：张新焕[1] 邓仰欣[1] 石昌红[1] 牛铭云[1] 丁鹤林[2] 

机构地区：[1]泰山医学院临床学院,山东泰安271000 [2]中山大学附属第二医院内分泌科,广东广州510120

出　　处：《中国病理生理杂志》2011年第7期1366-1371,共6页Chinese Journal of Pathophysiology

基　　金：泰山医学院青年科研基金科技计划资助项目(No.2006ZR029)

摘　　要：目的:探讨血管内皮生长因子(VEGF)936C/T突变与糖尿病视网膜病变(DR)的关系。方法:按WHO的糖尿病(DM)诊断和排除标准及分型标准,选取无亲缘关系的2型糖尿病患者254例,分为非增殖性视网膜病变(NPDR)组、增殖性视网膜病变(PDR)组和单纯2型糖尿病(DM)组,选取健康体检人群120例作为正常对照组(NC)。采用PCR-RFLP方法确定全部人员的基因型,对不同组间的临床与生化指标及VEGF浓度、936C/T多态性进行了统计分析。结果:NPDR和PDR组的CC基因型频率及C等位基因频率显著高于DM组(2=7.490,2=4.448,P<0.05;2=8.333,2=5.227,P<0.05)和NC组(2=9.934,2=4.899,P<0.05;2=10.895,2=5.714,P<0.05),而NPDR和PDR组(CT+TT)基因型频率及T等位基因频率显著低于NC组(2=9.934,2=10.895,P<0.01;2=4.899,2=5.714,P<0.05)和DM组(2=7.490,2=8.333,P<0.01;2=4.448,2=5.227,P<0.05)。DR多重危险因素分析显示血清低密度脂蛋白胆固醇(LDL-C)、总胆固醇(TC)、糖化血红蛋白(HbA1c)水平以及VEGF浓度和DR发病呈正相关,而VEGF936C/T突变与DR发病危险呈负相关(β=-1.027,OR=0.343,P<0.01,CI:0.157-0.723)。结论:中国汉族人群中存在VEGF936C/T突变。VEGF936C等位基因及CC基因型可能是中国汉族糖尿病患者易于发生DR的危险性遗传标志,而VEGF936T等位基因和携带T等位基因的基因型(936TT基因型和936CT基因型)可能是DR发病风险降低的遗传标志。血浆VEGF、LDL-C、TC和HbA1c水平可能是2型糖尿病患者易发DR的危险因素。AIM： To study the distribution of 936C/T polymorphism in 3＇-untranslated region of vascular endothelial growth factor（VEGF） gene in Chinese Han population and to analyze the relationship between the polymorphism and diabetic retinopathy（DR）.METHODS： Two hundred and fifty-four patients with type 2 diabetes mellitus recruited in this study were divided into NPDR group（non-proliferative diabetic retinopathy）,PDR group（proliferative diabetic retinopathy） and DM（diabetes without retinopathy） group.The normal control group consisted of 120 subjects.Genotypes were identified by PCR-RFLP among all the subjects,while other clinical parameters were measured.Serum levels of VEGF were tested by the method of ELISA.RESULTS： The frequencies of both genotype CC and allele C were significantly higher in NPDR group and PDR group than those in NC group（X2=9.934,X2=4.899,P0.05 and X2=10.895,X2=5.714,P0.05） and DM group（X2=7.490,X2=4.448,P0.05 and X2=8.333,X2=5.227,P0.05）.However,the frequencies of genotype（TT＋CT） and allele T were significantly lower in NPDR group and PDR group than those in NC group（X2=9.934,X2=10.895,P0.01 and X2=4.899,X2=5.714,P0.05） and DM group（X2=7.490,X2=8.333,P0.01 and X2=4.448,X2=5.227,P0.05）.Multivariate logistic regression analysis showed that the levels of glycohemoglobin（HbA1c）,total cholesterol（TC）,low-density lipoprotein cholesterol（LDL-C） and plasma VEGF presented a positive correlation with DR,respectively,and the 936C/T mutation of VEGF exhibited a negative correlation with DR（β=-1.027,OR=0.343,P0.01,CI： 0.157-0.723）.CONCLUSION： Allele 936C of VEGF may be a genetic marker susceptible to DR,while allele 936T may be a protective genetic marker of DR.The 936C/T mutation of VEGF may be a protective factor against DR.

关 键 词：血管内皮生长因子 基因多态性 糖尿病 2型 糖尿病视网膜病变 

分 类 号：R587.2[医药卫生—内分泌]