Association of LEPR Gene Polymorphisms With Youth-Onset Diabetes in Bangladesh

Introduction Polymorphisms of the leptin receptor (LEPR) gene are associated with type 2 diabetes mellitus (T2DM), but the association varies among different geographic populations. The present study aims to observe the association of single-nucleotide polymorphisms (SNPs) of the LEPR gene (rs1137100 and rs1137101) with youth-onset T2DM in Bangladesh. Methods This case-control study encompassed 62 individuals with youth-onset T2DM (age range 18-29 years) and an equal number of age-matched controls with normal glucose tolerance (NGT). Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Genotypes of both LEPR SNPs were expressed as AA, AG, and GG, where G is considered a risk allele. Results The frequency of G-allele was higher in DM than in NGT for both rs1137100 (55.6% (69/124) vs. 42.7% (53/124); OR 1.7, 95% CI 1.02-2.78; p=0.042) and rs1137101 (59.7% (74/124) vs. 41.9% (52/124); OR 95% CI 1.24-3.40, p=0.005). In the codominant model, the GG genotype was associated with DM (GG vs. AA: rs1137100: OR 3.37; CI 1.11-10.19; p=0.032; rs1137101: OR 4.93; CI 1.62-14.99; p=0.005) but not the AG genotype (AG vs. AA). In the dominant model, the risk variants AG+GG (vs. AA) of rs1137100 did not have an association (p=0.289), but rs1137101 had (OR 2.60; CI 1.07-6.33; p=0.035). In the recessive model, risk variant GG (vs. AG+AA) of both SNPs had an association with DM (rs1137100: OR 2.98; CI 1.19-7.47; p=0.017; rs1137101: OR 3.02; CI 1.25-7.27; p=0.014). No association was significant in any models when adjusted for body mass index (BMI). Conclusion Although the LEPR gene SNPs rs1137100 and rs1137101 show a potential association with an increased risk of youth-onset T2DM in the Bangladeshi population, this association appears to be BMI-dependent.