【作者】 王丽娜；

【导师】 张萍；

【作者基本信息】 大连医科大学 ， 内科学， 2011， 硕士

【摘要】 目的:本研究探讨PPARaV227A基因多态性在大连地区早发2型糖尿病组中的基因分布情况及其发病的相关性。方法:选取2型糖尿病受试者496例,男244例,女252例。正常对照组248例,男112例,女136例。以诊断年龄≤40岁定义为早发2型糖尿病,诊断年龄>40岁为晚发2型糖尿病。将2型糖尿病受试者分为早发2型糖尿病组206例,男126例,女80例,平均年龄36.33±4.02岁。晚发2型糖尿病组290例,男118例,女172例,平均年龄56.36±9.56岁。提取外周血白细胞DNA应用聚合酶链反应(PCR)检测PPARa基因V227A多态性并进行基因型和相关临床生化指标的比较。结果:①早发组FPG较高,TG显著升高,血尿酸较高。②PPARαV227A基因型频率在早发组、晚发组、对照组的分布。早发2型糖尿病组PPARαV227A基因型频率分布:VV、VA、AA分别为92.2%、7.8%、0%,V、A等位基因频率分别为92.2%、7.8%;晚发组VV、VA、AA基因型频率分别为83.1%、16.9%、0%,V、A等位基因频率分别为83.1%、16.9%;正常对照组基因型频率分布VV、VA、AA分别为85.9%、12.9%、1.2%。早发组与晚发组基因型及等位基因分布频率经检验后有显著性差异,携带227A等位基因降低患2型糖尿病风险;早发组与正常组基因型及等位基因分布频率经检验后有显著性差异,携带227A等位基因发生早发2型糖尿病的风险低;晚发组与对照组基因型及等位基因分布频率经检验后无统计学差异。③早发2型糖尿病组携带227A等位基因者较携带V227等位基因者TC、Apo-B水平低。晚发组及正常对照组中血脂水平差异无显著性。结论:①早发2型糖尿病组较晚发组血糖控制差、血脂及尿酸代谢紊乱更严重。②早发2型糖尿病组PPARαV227A变异率低于同地区晚发组及正常人群。③携带227A等位基因者TC、Apo-B水平较低,减少发生早发2型糖尿病的风险。④PPARα基因V227A多态性与早发2型糖尿病的血脂代谢紊乱有关。变异的227A等位基因为血脂异常的保护性因素。更多还原

【Abstract】 Objective: To explore the correlations of PPARαV227A polyphism in early-onset T2DM in dalian of China.Methods: A total of 496(244 men and 252 women ) T2DM subjects were enrolled and divided into two groups: early-onset and late-onset groups which were defined as diagnosed at≤40 and >40 years old. Early-onset T2DM subjects 206(126 men and 80 women) average age was 36.33±4.02 years old. Late-onset T2DM subjects 290(118 men and 172 women) average age was 56.36±9.56 years old.Normal control group subjects were composed of 248 healthy people (112 men and 136 women).Extracted peripheral blood white blood cell genomic DNA to detect PPARαV227A polymorphism.PCR-direct sequencing was employed to detect the PPARa V227A gene mutation in two groups and frequencies of genotype and allele were observed, and the clinical characteristics of mutation gene carriers were investigated.Results:①The fasting plasma glucose(FPG), triglyceride (TG), uric acid (UA) were higher in early-onset T2DM group than in late-onset T2DM group.②The overall frequencies ofVV VA AA in early-onset T2DM group and in late-onset T2DM group were 92.2%,7.8%, 0%, and 83.1 %, 16.9%,0%. In normal control group were85.9%, 12.9%,1.2%. The V227 allele frequency was 92.2%, and A227allele frequency was 7.8%in early-onset T2DM group,and the V227allele frequency was 83.1% and A227allele frequency was 16.9%in late-onset T2DM group. There were statistical differences in the gene type frequency and allele frequency distribution between the two groups.③In early-onset T2DM group A227allele had lower total cholesterol (TC)、Apo-B than V227allele.Conclusion:①The early-onset T2DM group had poorer blood glucose control, more severe dyslipidemia and higher uric acid when compared with the late-onset T2DM group.②In the early-onset T2DM group PPARαA227allele frequency was lower than in the late-onset T2DM group.③A227 variation was possibly protective factor for dyslipidemia. PPARαgene V227A polymorphism reduceded the risk of having early on-set T2DM by reducing the levels of TC and Apo-B.④PPARαgene V227A polymorphism was associated with earlyon-set T2DM dyslipidemia.It was a protective factor of dyslipidemia.更多还原