Association of TCF7L2 Polymorphisms with Susceptibility to Gestational Diabetes Mellitus: A Systematic Review and Meta-analysis

Background: Gestational diabetes mellitus (GDM) is a complex metabolic disorder of pregnancy with a strong genetic predisposition. GDM is associated with complications during pregnancy and increased risk of type 2 diabetes later in mothers and develops a vicious cycle of metabolic diseases for future generations. Evidence is accumulating that women with genetic variants at transcription factor 7-like 2 (TCF7L2) gene are more susceptible to GDM. The aim of the current meta-analysis was to assess the association of the TCF7L2 polymorphisms with GDM risk. Methods: PubMed, Web of Science, Embase, SID and CNKI databases were searched to identify relevant studies up to November 01, 2020. Using the fixed-effect or random-effect model, the pooled odds ratio and its corresponding 95% confidence interval were computed. Results: A total of 38 case-control studies including 24 studies with 6021 cases and 13289 controls on rs7903146, eight studies with 2404 cases and 2615 controls on rs12255372 and six studies with 1357 cases and 2858 controls on rs7901695 polymorphism were selected. Pooled data showed that there was a significant association between the TCF7L2 rs7903146, rs12255372 and rs7901695 polymorphisms and an increased risk of GDM in whole population. Stratified analysis showed that the TCF7L2 rs7903146 polymorphism was associated with GDM in Caucasian, mixed and Chinese women, but not in Asians. Moreover, the TCF7L2 rs12255372 polymorphism was associated with GDM in Asians and Caucasians women with GDM. Conclusion: The combined data indicated that the TCF7L2 rs7903146, rs12255372 and rs7901695 polymorphisms were associated with a significant risk of GDM in whole population, especially in Caucasian women.