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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。
Objective: To investigate the association and synergistic effect of UCP2 variant -866G / A and apolipoprotein E in Beijing population with diabetic nephropathy (DN). Methods: Genotyping was performed in 228 DN patients, 243 non-DN type 2 diabetes mellitus patients and 78 normal controls based on polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) Physical examination and biochemical determination. The data processing was completed by using SPSS (version16.0), and the representativeness of the population was evaluated by Hardy-Weinberg equilibrium test. According to the additive model, the overall distribution of genotype, recessive model and dominant model The associations of risk alleles and diseases were analyzed. Logistic regression was used to analyze the interaction between gene variants and stratified analysis to assess the contribution of their interactions to DN. Results: The additive model analysis showed that the distribution of UCP2 gene -866G / A between DN group and DM group was statistically significant (P <0.001). Further, through the explicit model, it was found that there was a positive correlation between -866A and DN, After sex and gender mix, the positive correlation still exists (OR = 1.814, 95% CI: 1.148-2.867). The interaction between UCP2 × APOE and DN has a positive correlation with age, gender, body mass index, blood glucose, triglyceride and other lipid indicators, and the synergistic effect exists between the two. Hierarchical analysis showed that UCP2 gene -866A was a risk factor for DN of independent APOEε4, and APOEε4 had an epistasis relationship with UCP2 gene -866A. CONCLUSION: The -860A allele of UCP2 gene and the APOEε4 allele are the risk alleles of DN in Beijing Han population. APOEε4 is heterodimeric and the two effects overlap.