天津医药

• 论著 •    

TCF7L2、AKT2、FOXO1基因多态性与2型糖尿病的相关性研究

张沫1,樊向维2,张捷1,3,刘德敏4   

  1. 1. 天津医科大学代谢病医院
    2. 天津医大代谢病医院
    3.
    4. 医科大学代谢病医院
  • 收稿日期:2012-02-06 修回日期:2012-06-28 出版日期:2012-12-15 发布日期:2012-12-15
  • 通讯作者: 张沫

The association study between polymorphisms on TCF7L2、AKT2、FOXO1 gene and Type 2 Diabetes

  • Received:2012-02-06 Revised:2012-06-28 Published:2012-12-15 Online:2012-12-15
  • Contact: ZHANG MO

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摘要： 探讨天津地区汉族人群WNT信号通路中TCF7L2、AKT2、FOXO1基因多态性与2型糖尿病发生的相关性。方法：随机选取352例2型糖尿病患者（T2DM）及176例健康对照者，提取基因组DNA，PCR扩增目的片段后，应用变性高效液相色谱技术检测三种基因的基因型频率，并选取不同峰型进行DNA测序。分析不同基因型频率的组间差异，并对联合基因型进行分析，Logistic回归分析相关危险因素。结果：Hardy-Weinberg平衡定律检测人群代表性良好（均P>0.05）。T2DM组和对照组中，AKT2基因的rs11669332位点的C/T杂合基因型频率分别为7.67%和3.41%，两组间差异无统计学意义(P>0.05)，TCF7L2基因rs12255372位点的G/T杂合基因型频率分别为18.5%和2.8%， FOXO1基因rs2701891位点C/C基因型频率分别为3.1%、1.1%，C/T基因型频率分别为21.3%、10.2%，两组间频率分布有统计学差异（P<0.01）。联合分析TCF7L2及FOXO1基因，TCF7L2 T+/ FOXO1T+、TCF7L2 G+/ FOXO1 C+按校正后a水准差异有统计学意义（P<0.004）。Logistic回归分析结果示糖化血红蛋白、尿素氮、TCF7L2 T+/ FOXO1C+为2型糖尿病的危险因素，高密度脂蛋白为保护因素。结论：TCF7L2基因的rs12255372位点G/T基因型携带者与FOXO1基因的rs2701891位点C/C、C/T基因型携带者发生T2DM危险性增大，且两基因间存在一定的协同作用，可能与天津地区汉族人群T2DM的发病有关，是2型糖尿病发生的危险因素。

关键词: 2型糖尿病, 基因多态性, 变性高效液相色谱

Abstract: To investigate the relationship between the different gene polymorphism in transcription factor 7-Like 2(TCF7L2) , protein kinase B(AKT2) and forkhead box transcription factor subgroupO1 (FOXO1)gene of the WNT signalling pathway, and the type 2 diabetes mellitus(T2DM) in Tianjin Han populations. Methods: 352 T2DM patients and 176 case controls were randomly enrolled in this study. After the genome DNA was extracted, genotype frequency was detected using the denaturing high performance liquid chromatography. And different peaks were sequenced. Then the differences of different genotype frequency between the groups were analyzed, and risk factors of T2DM were evaluated using logistic regression. Results: It’s a good representation of the population used the Hardy-Weinberg equilibrium testing (P>0.05). In the T2DM group and case control group, the C/T genotype frequency of rs11669332 in AKT2 gene are 7.67% and 3.41%,there is no different between the two groups. The G/T genotype frequency of rs12255372 in TCF7L2 gene are 18.5% and 2.8% , The C/C and C/T genotype frequency of rs2701891 in FOXO1 gene are 3.1%、1.1% and 21.3%、10.2%,respectively.There are significant differences( P<0.01). Significant differences of the TCF7L2 T+/ FOXO1T+、TCF7L2 G+/ FOXO1 C+ genotypes frequency exists in the conjoint analysis between the two groups After a standard calibration of a(P<0.004).The TCF7L2 T+/ FOXO1C+ genotype, glycosylated hemoglobin, urea nitrogen are the risk factors of T2DM, high density lipoprotein is a protective factor. Conclusion: This study indicates that G/T genotype in the TCF7L2 and the C/C,C/T genotype in the FOXO1 gene significantly contribute to T2DM susceptibility in Tianjin Han populations. A combined effect could be found between TCF7L2 and FOXO1. These two polymorphisms are the risk factors of T2DM.

Key words: ype 2 diabetes mellitus, gene polymorphism, denaturing high performance liquid chromatography