A gene variant in the transcription factor 7-like 2 (TCF7L2) is associated with an increased risk of gestational diabetes mellitus

Abstract

Objective: Adipokines play an important role in the pathogenesis of insulin resistance during pregnancy. We studied the association of genetic variants linked with type 2 diabetes in gestational diabetes mellitus (GDM) subjects and its influence on maternal adipokines.

Study design: We recruited 25 healthy pregnant women (Controls) and 45 women with GDM at 24-28 weeks of gestation. Maternal blood samples were collected at recruitment and delivery. Adipokines were determined at both sampling times. Genomic DNA was extracted from recruitment samples and FTO rs9939609, TCF7L2 rs4506565, rs7901695, rs12243326, rs12255372 and rs7903146, INSIG2 rs7566605, SREBF1 rs114001633, rs45535737 and rs12941356 and FATP4 rs2003560 genotyped.

Results: Serum adiponectin was significantly lower in GDM than Controls at recruitment and showed a similar trend at delivery (p=0.060). In contrast, resistin tended to higher levels in GDM only at recruitment. TCF7L2 rs4506565 (OR=2.31, 95% CI: 1.97-5.01; p=0.031) and FTO rs9939609 (OR=2.17, 95% CI: 1.07-4.41; p=0.039) were associated with GDM risk. Women carrying the T allele of TCF7L2 rs4506565 had increases in plasma resistin of 9.38 μg/L (95% CI 1.39-17.37; p=0.022) per allele; this association remained significant after adjusting for pre-gestational body weight.

Conclusion: TCF7L2 rs4506565 variant (T/T) is associated with increased risk of GDM and plasma resistin concentrations in women with GDM.

Keywords: Adiponectin; Gestational diabetes mellitus; Resistin; Single-nucleotide polymorphism; TCF7L2.