Analysis of the IRS1 G972R polymorphism showed that RR homozygosity was found exclusively in women with GDM (91.0, 8.3 and 0.7% vs 90.7, 9.3 and 0.0% for GG, GR and RR genotypes, respectively; p=0.014).
IRS-1 G972R was associated with the baseline characteristics of the patients with GDM, and might be related to insulin resistance that is seen in obese patients with GDM.
Our results showed a significant association between the three genetic variants and GDM risk, rs10830963 with a P-value less than 0.0001, rs1387153 with a P-value of 0.0002, and rs1801278 with a P-value of 0.001.
Thus, our data suggest that the common T2D susceptibility polymorphism of TCF7L2 (rs7903146 C/T) gene, and the G972R polymorphism of the IRS1 gene, seem to predispose to GDM in Greek women.
The minor alleles of rs7903146 (TCF7L2), rs12255372 (TCF7L2), rs1799884 (-30G/A, GCK), rs5219 (E23K, KCNJ11), rs7754840 (CDKAL1), rs4402960 (IGF2BP2), rs10830963 (MTNR1B), rs1387153 (MTNR1B) and rs1801278 (Gly972Arg, IRS1) were significantly associated with a higher risk of GDM.
We studied possible relations between GDM and both insulin receptor substrate 1 (IRS-1) (Gly972Arg) and beta3-adrenergic receptor (ADRB3 Trp64Arg, beta3-AR) gene mutations, considered potential modifying factors in the etiology of type 2 diabetes mellitus.
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).