Peroxisome proliferator-activated receptor Pro12Ala polymorphism and the risks of gestational diabetes mellitus: An updated meta-analysis of 12 studies.

BACKGROUND

Peroxisome proliferator-activated receptors-λ (PPAR-λ) is a member of nuclear receptor superfamily and acts as a ligand-dependent transcription factor often found in the adrenal gland, the spleen, and adipose tissue. The Pro12Ala polymorphism of PPAR-λ has been associated with the risks of gestational diabetes mellitus (GDM); however, association studies have provided conflicting results. The aim of this Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) compliant meta-analysis is to reach a more up-to-date and accurate estimation of the relationship between Pro12Ala genetic polymorphisms and the risks of GDM.

METHODS

Eligible studies were retrieved by searching PubMed, EMBASE, Web of Science, Ovid, WanFang, and Chinese National Knowledge Databases and selected according to a pre-defined inclusion criterion. The risk of bias was assessed using the Newcastle-Ottawa quality assessment scale. The per-allele odds ratio (OR) of risk allele proline (Pro) was compared between cases and controls in each study to describe the association between the Pro allele and an individual's risk of GDM. The ORs were pooled using both the random-effects model (the DerSimonian and Laird method) and the fixed effects model (the Mantel-Haenszel method) and the 95% confidence interval (95% CI) was calculated using Woolf method.

RESULTS

The final meta-analysis included a total of 11 articles of 12 data sets consisting of 7054 controls and 2980 GDM cases. Our results demonstrate that the Pro allele is not associated with GDM [OR: across multiple populations, 95% CI: 0.98-1.24; P(Z) = 0.01; P(Q) = 0.003]. In the stratified analysis by ethnicity, significantly increased risks were found for the Chinese (OR = 2.36; 95% CI: 1.47-3.78) and Korean (OR = 1.39; 95% CI: 1.00-1.93) populations.

CONCLUSION

These data suggest the potential role of Pro allele in the pathogenesis of GDM in Asian populations. Although the funnel plot of included studies showed assymetry, the results using the "trim and fill" method did not alter the conclusion of this study.