Association of risk variants for type 2 diabetes and hyperglycemia with gestational diabetes

Abstract

ObjectiveThe aim of this study was to investigate the association of risk variants for type 2 diabetes (T2D) and hyperglycemia with gestational diabetes (GDM).Design and methodsFive hundred and thirty-three Finnish women who were diagnosed with GDM and 407 controls with normal glucose tolerance during the pregnancy were genotyped for 69 single-nucleotide polymorphisms (SNPs) which have been previously verified as susceptibility risk variants for T2D and hyperglycemia. All participants underwent an oral glucose tolerance test at the follow-up study after the index pregnancy.ResultsRisk variants rs10830963 and rs1387153 ofMTNR1Bwere significantly associated with GDM (odds ratio (OR)=1.62 (95% CI 1.34–1.96),P=4.5×10−7and 1.38 (1.14–1.66),P=7.6×10−4respectively). Both SNPs ofMTNR1Bwere also significantly associated with elevated fasting glucose level and reduced insulin secretion at follow-up. Additionally, risk variants rs9939609 ofFTO, rs2796441 ofTLE1, rs560887 ofG6PC2, rs780094 ofGCKR, rs7903146 ofTCF7L2and rs11708067 ofADCY5showed nominally significant associations with GDM (OR range from 1.25 to 1.30).ConclusionsOur study suggests that GDM and T2D share a similar genetic background. Our findings also provide further evidence that risk variants ofMTNR1Bare associated with GDM by increasing fasting plasma glucose and decreasing insulin secretion.