Maternal genetic contribution to pre-pregnancy obesity, gestational weight gain, and gestational diabetes mellitus

IntroductionPre-pregnancy obesity, gestational diabetes mellitus (GDM), and gestational weight gain (GWG) are associated with each other. This is the first study to investigate whether genetic variants were associated with having GDM, and whether genetic variants-related GDM were associated with adiposity including pre-pregnancy obesity and excessive GWG in Turkish women.Patients and methodsWomen with GDM (n=160) and without GDM (n=145) were included in case-controlled study. Genotyping of the HNF1A gene (p.I27L rs1169288, p.98V rs1800574, p.S487N rs2464196), the VDR gene (p.BsmI rs1544410, p.ApaI rs7975232, p.TaqI rs731236, p.FokI rs2228570), and FTO gene (rs9939609) SNPs were performed by using RT-PCR.ResultsThe FTO AA genotype was associated with an increased risk of having GDM (AA vs. AT+TT, 24.4% vs. 12.4%, OR=2.27, 95% CI [1.23-4.19], p=0.007). The HNF1A p.I27L GT/TT genotype was associated with increased GDM risk (GT+TT vs. GG-wild, 79.4% vs. 65.5%, OR=2.02, 95% CI 1.21-3.38], p=0.007). However, all VDR gene SNPs and the HNF1A p.A98V, p.S487N were not associated with having GDM (p>0.05). The FTO AA genotype was associated with an increased risk for pre-pregnancy overweight/obesity (OR=1.43, 95% CI [1.25-3.4], p=0.035), but not associated with excessive GWG after adjusting for pre-pregnancy weight (p>0.05). Pre-pregnancy weight, weight at delivery, and GWG did not differ in both VDR and HNF1A gene carriers (p>0.05). HOMA-IR and HbA1c were increased in both p.I27L TT and FTO AA genotype carriers (p<0.05).ConclusionThe adiposity-related gene FTO is associated with GDM by the effect of FTO on pre-pregnancy obesity. The diabetes-related p.I27L gene is associated with GDM by increasing insulin resistance.