Endocrine Abstracts

Background: Gestational diabetes mellitus (GDM) is a risk factor for type 2 diabetes and both conditions are characterized by insulin resistance (IR) and decreased insulin production by pancreatic beta-cells. FNDC5 gene encodes a type I membrane protein that is proteolytically processed to form a hormone secreted into the blood, termed irisin. After induction by exercise, irisin activates profound changes in the subcutaneous adipose tissue, stimulating browning and UCP1 gene expression. This causes a significant increase in total body energy expenditure and resistance to obesity-linked IR. Studies have shown that circulating irisin is decreased in women with GDM and the FNDC5 gene is also expressed in the human placenta. Thus, genetic variants in FNDC5 gene may be associated with DGM.

Objective: To evaluate if the polymorphisms rs3460A/G and rs1746661G/T in the FNDC5 gene are associated with GDM and/or its clinical features.

Methods: We analyzed 132 pregnant women without GDM (controls) and 219 pregnant women with GDM (cases). Polymorphisms were genotyped by Real-Time PCR using TaqMan MGB probes. Haplotypes constructed from the combination of rs1746661 and rs3480 polymorphisms were inferred using the Phase 2.1 program.

Results: Genotype and allele frequencies of the rs1746661 and rs3480 polymorphisms did not differ significantly between cases and controls (P>0.05). The haplotype frequencies also did not differ between the two groups (P=0.913). Interestingly, patients carrying the T allele of the rs1746661 polymorphism had higher values of systolic blood pressure (SBP) than patients with the A/A genotype (127.2±18.7 vs 122.9±17.3 mm/Hg; P=0.004), adjusting for the use of antihypertensive medications.

Conclusion: This study showed no association between the rs1746661 and rs3480 polymorphisms and GDM; however, the rs1746661T mutated allele seems to be associated with increased SBP in pregnant women independently of GDM.