Study of Leptin RS2167270 Gene Polymorphism in Women Diagnosed with Gestational Diabetes Mellitus

Abstract

Background: Gestational diabetes mellitus (GDM) is a complex metabolic disorder influenced by multiple genetic and environmental factors. Recent evidence indicates that variations in the leptin gene may contribute to altered metabolic regulation during pregnancy and increase susceptibility to GDM.

Aim: To assess the association between leptin rs2167270 gene polymorphism and gestational diabetes mellitus in Indian women.

Methods: This hospital-based case-control study included 190 pregnant women, comprising 95 GDM cases and 95 healthy controls. Clinical and biochemical parameters including fasting glucose, insulin, HbA1c, and lipid profile were measured. Genomic DNA was extracted from peripheral blood, and rs2167270 genotyping was performed using the TaqMan® SNP assay on Insta Q 96 platform. Genotype frequencies were compared using Chi-square tests, and logistic regression was applied to estimate GDM risk.

Results: The distribution of rs2167270 genotypes differed significantly between groups, with the mutant homozygous GG genotype observed more frequently in GDM women (29.5%) than in controls (18.9%). The overall genotype comparison (3×2) was statistically significant (χ² = 6.86, p = 0.032), suggesting a genetic predisposition. Within the GDM cohort, biochemical parameters showed a progressive deterioration from AA to AG to GG genotypes. GG carriers had significantly higher fasting glucose, fasting insulin, HbA1c, and LDL-C levels, along with lower HDL-C, indicating increased insulin resistance and dyslipidemia. Logistic regression demonstrated that the GG genotype was associated with more than a twofold increased risk of GDM compared to AA, even after adjustment for confounders.

Conclusion: The leptin rs2167270 polymorphism shows a significant association with both the development and metabolic severity of GDM. The GG genotype may serve as a potential genetic marker for early identification of women at increased risk, supporting future advances in personalized prediction and targeted management of GDM.