Lack of associations between the FTO polymorphisms and gestational diabetes: A meta-analysis and trial sequential analysis

Abstract

Background: Molecular epidemiological studies have sought associations between Fat mass and obesity associated (FTO) gene polymorphisms and gestational diabetes mellitus (GDM) risk, but findings are inconsistent. Hence, we performed a meta-analysis to clarify this problem.

Methods: Case-control studies reporting the relationship of three FTO polymorphisms (rs9939609, rs8050136, and rs1421085) and GDM published before June 2018 were searched in 6 electronic databases such as PubMed and Embase. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. Trial sequential analysis (TSA) was performed to evaluate the type 1 and type 2 errors.

Results: A total of 5 studies involving 703 GDM cases and 2700 controls for rs9939609, 3 studies involving 1144 GDM cases and 909 controls for rs8050136, and 2 studies involving 207 GDM cases and 205 controls for rs1421085, were included in the meta-analysis. No association was observed between the three polymorphisms with the GDM risk under all genetic models. For example, the ORs and its 95% CIs under dominant genetic model were 0.88 (0.59, 1.33) for rs9939609, 1.11 (0.91, 1.35) for rs8050136, and 0.91 (0.58, 1.41) for rs1421085, respectively. Under TSA, there are insufficient levels of evidence for all of these three polymorphisms.

Conclusion: The present meta-analysis provides statistical evidence indicating a lack of association between FTO polymorphismsand GDM risk. More studies with larger sample size are needed to confirm these null associations.

Keywords: Fat mass and obesity associated gene; Gestational diabetes; Meta-analysis; Polymorphisms; Trial sequential analysis.