Hba1c levels are increased in patients with gestational diabetes carrying the T/T genotype of the rs1990760 polymorphism in the IFIH1 gene

Abstract

Background: Gestational diabetes mellitus (GDM) is diabetes diagnosed in the second or third trimester of pregnancy that is not clearly overt diabetes. This condition is a common complication of pregnancy, being associated with both maternal and neonatal adverse outcomes. Several studies have indicated that viruses play an important role in the pathophysiology of diabetes. IFIH1/MDA5 gene encodes a cytoplasmic receptor that recognizes viral nucleic acids, playing a major role in the immune response against viruses. Accordingly, the rs1990760 (G/A) polymorphism in the IFIH1 gene has been associated with type 1 diabetes mellitus in different populations. Considering that the MDA5 receptor is expressed in human placenta, we therefore hypothesized that the rs1990760 G/A polymorphism could be also associated with GDM. Objectives: To investigate the association between the IFIH1 rs1990760 polymorphism and GDM and/or its clinical characteristics in a Southern Brazilian population. Moreover, we aimed to analyze IFIH1 expression in placentas from GDM patients and healthy pregnant women according to different rs1990760 genotypes. Materials and methods: We analyzed 129 patients with GDM (cases) and 144 pregnant women without GDM (controls). The polymorphism was genotyped by RT-PCR using TaqMan MGB probes (Life Technologies). IFIH1 expressions in placentas from 70 cases and 36 controls were evaluated using RT-qPCR. Results: Genotype and allele frequencies of the rs1990760 polymorphism did not differ between GDM patients and nondiabetic controls (P=0.702 and P=0.708, respectively), and adjustment for ethnicity did not change these Results. In GDM patients, fasting glucose levels, body mass index and age were not significantly different between rs1990760 genotypes. However, T/T genotype carriers had increased levels of glycated hemoglobin (A1c) as compared to G allele carriers (5.9 ± 0.4 vs. 5.4 ± 0.5, P=0.007). IFIH1 expression in placenta was similar among the three genotypes of the rs1990760 polymorphism (P>0.05). Interestingly, IFIH1 expression in placenta was decreased in patients with GDM as compared to controls (7.0 ± 4.2 vs. 9.7 ± 9.4, P=0.044). Accordingly, IFIH1 expression was inversely correlated to A1c levels (r=0.549, P=0.035). Conclusions: This study suggests an association between the T/T genotype with increased levels of A1c. Furthermore, IFIH1 gene expression seems to be associated with protection for GDM, and it was inversely correlated to A1c levels.