中文摘要：

目的：探讨解耦联蛋白2基因（UCP2）启动子变异-866G/A及载脂蛋白E与北京人群糖尿病肾病（DN）的发生关联和协同效应。方法：基于聚合酶链式反应-限制性片段长度多态性（PCR-RFLP）技术,对228例DN患者,243例非DN的2型糖尿病患者及78例正常对照进行基因分型,同时进行体格检查和生化指标测定,数据处理使用SPSS（version16.0）完成,用Hardy-Wein-berg平衡检验评价人群代表性,按照加性模型分析基因型的整体分布规律,隐性模型和显性模型分析风险等位基因与疾病的关联,通过Logistic回归分析基因变异间的交互作用,分层分析评估其相互作用对DN的贡献。结果：加性模型分析提示UCP2基因-866G/A在DN组和DM组间的分布差异达到统计学显著性（P〈0.001）,进一步通过显性模型发现-866A同DN存在正关联,调整年龄和性别混杂后,正关联仍然存在（OR=1.814,95%CI：1.148-2.867）。UCP2×APOE交互项和DN存在独立于年龄、性别、体质指数、血糖、甘油三酯等血脂指标的正关联,二者存在效应的协同作用。分层分析表明UCP2基因-866A是独立APOEε4的DN的危险因素,且APOEε4对UCP2基因-866A存在异位显性（epistasis）关系。结论：UCP2基因启动子-866A等位基因和APOEε4等位基因是北京汉族人群DN的风险等位基因,APOEε4存在异位显性,二者效应存在叠加。

英文摘要：

Objective：To investigate the relationship and synergistic effect between uncoupling protein 2（UCP2） gene promoter-866 G/A and apolipoprotein E for the risk of diabetic nephropathy（DN）.Methods：Based on polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP）,228 DN patients,243 type 2 diabetic cases without DN and 78 normal controls were genotyped,physical examination and the biochemical indicators determined,and the data were processed using SPSS（version16.0）.The Hardy Weinberg equilibrium was tested for the population representative and tested the overall distribution under additive model.Association under recessive and dominant models was tested to investigate the potential relationship between risk allele and disease.The Logistic regression analysis was performed to test the gene-gene interaction and their contribution for DN was tested by stratifying analysis.Results：There were significant differences for UCP2 gene-866 G/A genotypes between DN and DM group（P 0.001）,and there was positive association with DN under dominant model.Even after adjusted for the age and sex confounding,it still existed（OR = 1.814,95% CI：1.148 2.867）.The UCP2×APOE interaction seemed existed independent of age,sex,BMI,glucose,lipid such as TG,which suggested an effect of synergy.The stratifying analysis showed that UCP2-866A was a risk factor for DN independent of APOE ε4,and there was epistasis between them.Conclusion：The-866A allele in UCP2 promoter and APOEε4 were both risk factors for DN in Beijing Hans and an epitasis effect of APOEε4 was detected between them in the synergetic contribution for the susceptibility of DN.