Association of BDNF polymorphism with gestational diabetes mellitus risk: A novel insight into genetic predisposition

Objectives: Gestational diabetes mellitus (GDM) is a prevalent metabolic disorder during pregnancy with potential long-Term health implications for the mother and child. The interplay between genetics and GDM susceptibility remains an area of active research. Recently, brain-derived neurotrophic factor (BDNF) was investigated in relation to obesity and impaired glucose metabolism and pathogenesis. We aimed to investigate the association of common BDNF polymorphisms, with GDM risk in Israeli females. Methods: A cohort of 4,025 Israeli women data for BDNF common SNPs was analyzed for potential association with GDM using binary logistic regressions analysis (SPSS 29.0 and R) adjusted for confounding variables (age, T1DM, T2DM, PCOS) under different genetic models. Results: The GDM and Non-GDM genetic frequencies for the BDNF rs925946 Tag-SNP were significantly different. The genetic frequencies were 54.16%, and 66.91% for the wild type (GG), 38.88 and 29.64% for the heterozygotes (TC), and 6.94 and 3.48% for the risk allele homozygotes (TT) for the GDM non-GDM populations, respectively. Carriers of BDNF rs925946 were significantly associated with higher risk for GDM, following the dominant genetic model (OR=1.7, 95% CI 1.21-2.39, p=0.002), the recessive genetic model (OR=2.05, 95% CI 1.04-4.03, p=0.03), and the additive genetic model (OR=1.62, 95% CI 1.13-2.3, p=0.008). This association persisted after adjusting for age, T1DM, T2DM, and polycystic ovary syndrome (PCOS). Conclusions: Carrying BDNF rs925946 polymorphism predisposes to a higher risk of GDM pathogenesis. Its role and implications warrant further investigation, especially when considering preventive measures for GDM development.