Shayedat-Ullah Md, Sultana Nusrat, Hasan Mashfiqul, Amin U S Mahzabin, Rahman Tahaia Anan, Roy Indira, Rayhan Mukul, Sutradhar Palash Chandra, Salimullah Md, Hasanat Muhammad Abul
Endocrinology, Bangladesh Medical University, Dhaka, BGD.
Molecular Biotechnology Division, National Institute of Biotechnology, Dhaka, BGD.
Cureus. 2025 May 23;17(5):e84696. doi: 10.7759/cureus.84696. eCollection 2025 May.
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.
引言
瘦素受体（LEPR）基因多态性与2型糖尿病（T2DM）相关，但这种关联在不同地理人群中有所不同。本研究旨在观察LEPR基因单核苷酸多态性（SNP，rs1137100和rs1137101）与孟加拉国青年发病型T2DM的关联。
方法
本病例对照研究纳入了62例青年发病型T2DM患者（年龄范围18 - 29岁）以及数量相等的年龄匹配的糖耐量正常（NGT）对照。通过聚合酶链反应 - 限制性片段长度多态性（PCR - RFLP）进行基因分型。两个LEPR SNP的基因型表示为AA、AG和GG，其中G被视为风险等位基因。
结果
对于rs1137100，糖尿病组G等位基因频率高于NGT组（55.6%（69/124）对42.7%（53/124）；OR 1.7，95% CI 1.02 - 2.78；p = 0.042），对于rs1137101也是如此（59.7%（74/124）对41.9%（52/124）；OR 95% CI 1.24 - 3.40，p = 0.005）。在共显性模型中，GG基因型与糖尿病相关（GG对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），但AG基因型与糖尿病无关（AG对AA）。在显性模型中，rs1137100的风险变异AG + GG（对AA）无关联（p = 0.289），但rs1137101有（OR 2.60；CI 1.07 - 6.33；p = 0.035）。在隐性模型中，两个SNP的风险变异GG（对AG + AA）与糖尿病相关（rs1137100：OR 2.98；CI 1.19 - 7.47；p = 0.017；rs1137101：OR 3.02；CI 1.25 - 7.27；p = 0.014）。调整体重指数（BMI）后，在任何模型中均无显著关联。
结论
尽管LEPR基因SNP rs1137100和rs1137101显示出与孟加拉国人群青年发病型T2DM风险增加存在潜在关联，但这种关联似乎依赖于BMI。
