【作者】 回园敕；

【导师】 向红丁； 黎明；

【作者基本信息】 中国协和医科大学 ， 内分泌代谢学， 2008， 博士

【摘要】 研究目的遗传学和流行病学研究均表明,妊娠糖尿病和2型糖尿病之间具有一定的相关性,二者均是多基因多因素所致的疾病,以胰岛素抵抗和胰岛素分泌功能受损为特征。最近发现,TCF7L2基因多态性与2型糖尿病显著关联。本次实验旨在研究TCF7L2基因的rs290487C/T、rs11196205C/G和rs11196218A/G在妊娠糖尿病孕妇和正常孕妇中的分布频率,探讨TCF7L2基因在妊娠糖尿病遗传易感性中的作用。研究方法本次实验共收集受试者1140例,其中50g葡萄糖负荷试验(GCT)正常者274例,GCT阳性受试者866例,GCT阳性受试者进一步行100g口服葡萄糖耐量试验(OGTT),其中正常373例,IGT患者158例,GDM患者335例,将GCT阴性与NGT者合并为对照组,IGT与GDM者合并为病例组。在所有受试者中用连接酶检测反应确定基因型。结果1.在所有受试者中,TCF7L2基因rs290487C/T位点CC、CT及TT三种基因型分布频率分别为16.02%、45.18%及38.79%;rs11196205C/G位点GG、CG基因型分布频率为95.46%、4.54%,未发现CC基因型者;rs11196218A/G位点AA、AG及GG基因型分布频率分别为6.66%、41.70%及51.64%。2.TCF7L2基因rs290487C/T在病例组中三种基因型分布与对照组比较,差异有显著性(x~2=6.490,P=0.039);CC+CT基因型频率在病例组中显著高于对照组(x~2=4.082,P=0.043),病例组的C等位基因频率高于对照组,两者比较有统计学意义(x~2=6.358,P=0.0117);rs11196205C/G及rs11196218A/G位点各基因型分布及等位基因频率在病例组和对照组间无差别。3.TCF7L2基因rs290487C/T、rs11196205C/G和rs11196218A/G位点各基因型间临床资料及生化指标比较,差异未见显著性。4.三个位点的连锁不平衡分析显示,rs11196205及rs11196218两个位点不完全连锁(D’=0.218),rs11196205与rs290487两点亦是不完全连锁(D’=0.345)。5.Logistic回归分析显示,TCF7L2基因rs290487的CC基因型者发生妊娠糖尿病的危险是T等位基因携带者的1.23倍,年龄、糖尿病家族史、体质指数、超敏C反应蛋白均为发生高血糖的独立危险因素。结论TCF7L2基因rs290487C/T、rs11196205C/G和rs11196218A/G位点在中国汉族人群中存在多态性;rs290487位点CC+CT基因型频率在妊娠糖尿病组中明显高于正常孕妇组,CC基因型是血糖升高的危险因素。更多还原

【Abstract】 ObjectiveGenetic and epidemiological studies suggest an association between gestational diabetes mellitus and type 2 diabetes.Both are polygetic multifactorial disorders characterized by beta cell dysfunction and insulin resistance.Gene polymorphisms of the transcription factor 7-like 2(TCF7L2) gene have been reported to be associated with type 2 diabets mellitus.Our aim was to investigate whether common genetic variants that have previously been associated with type 2 diabetes or related phenotypes would also confer risk for gestational diabetes mellitus.MethodsIn 1140 unrelated pregnant Chinese women(493 women with gestational diabetes mellitus, 647 non-diabetic control subjects) we genotyped the transcription factor 7-like 2 rs290487, rs11196205 and rs11196218 using ligase detection reaction.ResultsThe CC,CT and TT genotype frequencies of TCF7L2 rs290487 position in Beijing residents were 16.02%、45.18%and 38.79%;And the frequency of GG and CG genotype of TCF7L2 rs11196205 position were 95.46%、4.54%;And the frequency of AAAG and GG genotype of TCF7L2 rs11196218 position were 6.66%、41.70%及51.64%.The CC,CT and TT genotype frequencies of the TCF7L2 rs290487 variant differed significantly between women with gestational diabetes mellitus and control women(18.75%,45.83%and 35.42%vs 13.95%, 44.69%and 41.36%,x~2=6.49,p=0.039).Homozygous(CC-genotype) and heterozygous (CT-genotype) carriers in gestational diabetes mellitus group were higher than those in non-GDM group(x~2=4.082,P=0.043).Compared with T-allele carriers,the CC-genotype carriers had a 1.23-fold(95%CI 1.021-1.962,p=0.042) increased risk of gestational diabetes mellitus.NO differences of the genotype and allelic frequencies at rs11196205 and rs11196218 were observed between the cases and the controls.ConclusionsThere were polymorphisms of the transcription factor 7-like 2 gene rs290487C/T,rs11196205C/G and rs11196218A/G in Chinese population from Beijing residents.Homozygous(CC-genotype) and heterozygous(CT-genotype) carriers of TCF7L2 rs290487 variant in gestational diabetes mellitus group were higher than those in non-GDM group.The TCF7L2 rs290487 variant is associated with an increased risk of gestational diabetes mellitus in Chinese women.更多还原