Genetic variants associated with gestational diabetes mellitus: a meta-analysis and subgroup analysis

Previous studies have demonstrated that gestational diabetes mellitus (GDM) and Type 2 diabetes mellitus (T2D) share common genetic polymorphisms. We conducted meta-analysis and subgroup analysis of all available variants and determined the effects of confounding and experimental components on the genetic association of GDM. Any case-controlled or cohort studies with genotype distribution compared GDM cases with controls were included. In total, 28 articles including 8,204 cases and 15,221 controls for 6 polymorphisms were studied. rs10830963( MTNR1B ), rs7903146( TCF7L2 ), and rs1801278( IRS1 ) were significantly associated with the increased GDM risk. The association of rs4402960( IGF2BP2 ) and rs1800629( TNF-α ) was significant only when the studies with control allele frequency deviation and publication bias were excluded. Further subgroup analysis showed the risk alleles of rs7903146( TCF7L2 ) and rs1801282( PPARG ) were significantly associated with the GDM risk only in Asian, but not in Caucasian population. The OGTT test using 100 g, but not 75 g; and genotype detection by other assays, but not Taqman method, were also significantly associated with increased GDM risk in rs1801278( IRS1 ) and rs7903146( TCF7L2 ). Overall GDM was associated with rs10830963( MTNR1B ), rs7903146( TCF7L2 ), and rs1801278( IRS1 ), but only rs7903146( TCF7L2 ) and rs1801282( PPARG ) were significant in Asian populations. While rs1801278( IRS1 ) and rs7903146( TCF7L2 ) were significantly affected by OGTT protocol and genotyping methods.