| Objective:To explore the association between gene polymorphism of transcription factor 7-like 2（TCF7L2）and gestational diabetes mellitus（GDM）susceptibility.Methods:A case-control design was used in this study,843 pregnant women who were diagnosed GDM were included in the case group,and 877 pregnant women without GDM were included in the control group,1720 participants were included in the study totally.General information of the participants was collected through questionnaire survey,and TCF7L2 gene rs11196218,rs4506565,rs7895340,rs7901695,rs11196205,rs12243326 and rs290487 were genotyped by the Agena Mass ARRAY system.The association between TCF7L2 gene polymorphism and GDM susceptibility,the potential functional role of each locus in the gene expression of islet cells,and the cumulative effect of risk genotypes on GDM susceptibility were conducted by SPSS25.0 software and Roadmap Database.Results:1.This study confirmed that pregnant women who were older（OR=1.13,95%CI:1.1-1.16）,with higher pre-pregnancy BMI（OR=1.12,95%CI:1.07-1.16）or a family history of T2DM（OR=2.51,95%CI:1.88-3.35）were more likely develop into GDM.2.rs4506565（AT vs.AA,OR=1.89,95%CI:1.18-3.02）,rs7895340（GA vs.GG,OR=1.93,95%CI:1.06-3.54）,rs7901695（TC vs.TT,OR=1.79,95%CI:1.11-2.88）and rs11196205（GC vs.GG,OR=2.15,95%CI:1.16-3.98）polymorphisms were all associated with GDM susceptibility.3.The pregnant women’s polymorphism of rs4506565,rs7901695,rs7895340,rs11196205 and rs12243326 of TCF7L2 gene was associated with 1-hour OGTT and/or 2-hour OGTT glycemia level significantly（P（27）0.05,all）,but not with fasting plasma glucose level（P（29）0.05,all）.4.The rs4506565,rs7895340,rs7901695,and rs11196205 of TCF7L2 gene were all located in human islet functional elements,and the variation of these locus may affect the function of islet cells by affecting the methylation and acetylation of histone in islet cells.5.There was a cumulative effect on the risk of GDM between the risk genotypes of TCF7L2 locus.With the increased of the number of risk genotypes in pregnant women,the risk of developing GDM in pregnant women tended to increase(x2trend=8.030,P=0.005).The risk of developing GDM was 3.51 times（95%CI:1.38-8.90）for pregnant women with four risk genotypes compared with those without risk genotype.And the risk of developing GDM of the pregnant women with two or more risk genotypes was 1.69times（95%CI:1.11-2.57）compared with those without or with only one risk genotype.Conclusion:Polymorphism of rs4506565,rs7895340,rs7901695 and rs11196205 of TCF7L2 is associated with GDM susceptibility,but no correlations have been found between polymorphism of rs11196218,rs12243326 and rs290487 and the susceptibility of GDM. |
