Association of common polymorphisms with gestational diabetes mellitus in Japanese women: A case-control study

Abstract

Gestational diabetes (GDM) and type 2 diabetes (T2DM) share part of pathomechanism and several T2DM susceptibility genes are demonstrated to be associated with GDM. No information on the genetics of GDM, however, was available in Japanese women. In this study, T2DM risk variants (45 single nucleotide polymorphisms [SNPs] from 36 genes) identified in previous studies were genotyped using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in a cohort of 171 Japanese women with GDM and 128 normal glucose tolerance (NGT) diagnosed by the new International Association of Diabetes in Pregnancy Study Group criteria. Of 45 SNPs, three genetic variants were nominally associated with the development of GDM: rs266729 (p = 0.013, odds ratio [OR]: 1.56, 95% confidence interval [CI]: 1.10-2.23) in ADIPOQ, rs10811661 (p = 0.035, OR: 1.46, 95% CI: 1.03-2.08) in CDKN2A/2B, and rs9505118 (p = 0.046, OR: 1.41, 95% CI: 1.01-1.97) in SSR1-RREB1. There was a significant difference in the number of risk alleles of three variants between women with GDM and NGT (3.79 ± 1.33 vs. 3.05 ± 1.41, p = 6.0 × 10^-6). In combined analysis of three genetic variants, women with five or more risk alleles had a 7.32-fold increased risk of GDM (p = 5.6 × 10^-5, 95% CI: 4.54-11.96), compared with those having no more than one risk allele. Our results suggest several risk variants of T2DM had cumulative effects on the development of GDM in Japanese women.