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

TL;DR

This study finds that certain genetic variations in the LEPR gene may be linked to youth-onset diabetes in Bangladesh, but the link depends on body mass index.

Contribution

The study identifies specific LEPR gene polymorphisms associated with youth-onset T2DM in a Bangladeshi population.

Findings

The G-allele frequency of rs1137100 and rs1137101 was higher in diabetes patients than controls.

The GG genotype of both SNPs was associated with diabetes in codominant and recessive models.

The association between SNPs and diabetes was not significant after adjusting for BMI.

Abstract

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.

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