Adipose tissue mRNA expression analyses of insulin signalling genes: <i>PI3KCA, PI3KR1, IRS1 and IRS2</i> showed significantly decreased <i>PI3KR1</i> expression (-23%) in visceral fat in GDMwith no association to promoter DNA methylation.
The rs13266634/T (SLC30A8, OR = 0.74/0.71, p = 0.05/0.02) and rs7578326/G (LOC646736/IRS1, OR = 0.62/0.60, p = 0.001/0.006) variants were associated with lower risk to develop GDM.
In addition, more severe IR was observed in the placenta of GDM patients than the control group, evidenced with higher pIRS-1(ser312) (p<0.001) and lower IRS-1 (p<0.05) as well as pAkt proteins (p<0.01).
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).
In conclusion, our study found that the genetic polymorphisms rs10830963 and rs1387153 in MTNR1B and rs1801278 in IRS1 were associated with an increased risk of developing GDM.
The aim of the present study was to scrutinize the relationship between the G972R polymorphism of the insulin receptor substrate-1 (IRS-1) gene with GDM in the Saudi female population.
The minor alleles of rs7903146 (TCF7L2), rs12255372 (TCF7L2), rs1799884 (-30G/A, GCK), rs5219 (rs5219" genes_norm="3767">E23K, KCNJ11), rs7754840 (CDKAL1), rs4402960 (IGF2BP2), rs10830963 (MTNR1B), rs1387153 (MTNR1B) and rs1801278 (rs1801278" genes_norm="3667">Gly972Arg, IRS1) were significantly associated with a higher risk of GDM.
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.
There was a significant increase in insulin receptor (IR) substrate (IRS)-1 protein expression with a concurrent decrease in IRS-2 protein expression in non-obese women with insulin-controlled GDM compared with diet-controlled GDM and normal controls.
The X-Arg genotype of IRS-1 was significantly associated with a positive family history of diabetes in NGT (P = .006) and neared significance in GDM (P = .057).
IRS-1G972R 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.
Analysis of the IRS1G972R 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).