Hameed Iqra, Masoodi Shariq R, Afroze Dil, Bhat Riyaz A, Naykoo Niyaz A, Mir Shahnaz A, Mubarik Idrees, Ganai Bashir A
Department of Biochemistry, University of Kashmir, Srinagar, India.
Department of Endocrinology, Sher-I-Kashmir Institute of medical Sciences, Srinagar, Kashmir India.
J Diabetes Metab Disord. 2014 Dec 20;13(1):124. doi: 10.1186/s40200-014-0124-z. eCollection 2014.
Type 2 diabetes mellitus is a multi-factorial disease in which both genetic and non-genetic factors interact in order to precipitate the diabetic phenotype. Among various predisposing genetic loci, a pentanucleotide (CTTTA) Del/Ins variant in the 3'-UTR of the LEPR gene is associated with type 2 diabetes and its related traits. This study was done to explicate for the first time the association of this Del/Ins polymorphism of LEPR gene in type 2 diabetes patients belonging to the ethnic population of Kashmir valley.
670 unrelated subjects comprising of 320 type 2 diabetes patients and 350 healthy controls were included in the study. Genotyping of the untranslated region of LEPR gene encompassing this Del/Ins variant was done by PCR-RFLP technique and results were validated by direct sequencing.
Genotype frequencies for both type 2 diabetes cases and healthy controls were consistent with Hardy-Weinberg equilibrium (χ(2) = 3.09 and 2.37, P = NS). The Del/Del genotype was predominantly found in cases than controls (P = 0.003, OR: 0.62, CI: 0.45-0.85). Carriers of Ins/Ins genotype were relatively protected against the risk factors (P = 0.0004, OR: 0.31, 95% CI: 0.15-0.61). A positive association was observed between the Del allele and the risk factors of type 2 diabetes.
The results elucidate that the CTTTA Del allele is a genotypic risk factor of type 2 diabetes in the Kashmiri population.
2型糖尿病是一种多因素疾病，其中遗传和非遗传因素相互作用以促成糖尿病表型。在各种易感基因位点中，LEPR基因3'-UTR中的五核苷酸（CTTTA）缺失/插入变异与2型糖尿病及其相关特征有关。本研究首次旨在阐明克什米尔山谷族裔人群的2型糖尿病患者中LEPR基因这种缺失/插入多态性的关联。
本研究纳入了670名无亲缘关系的受试者，包括320名2型糖尿病患者和350名健康对照。通过PCR-RFLP技术对包含该缺失/插入变异的LEPR基因非翻译区进行基因分型，并通过直接测序验证结果。
2型糖尿病病例组和健康对照组的基因型频率均符合哈迪-温伯格平衡（χ(2) = 3.09和2.37，P = 无显著差异）。缺失/缺失基因型在病例组中的比例高于对照组（P = 0.003，OR：0.62，CI：0.45 - 0.85）。插入/插入基因型的携带者相对受到危险因素的保护（P = 0.0004，OR：0.31，95% CI：0.15 - 0.61）。观察到缺失等位基因与2型糖尿病危险因素之间存在正相关。
结果表明，CTTTA缺失等位基因是克什米尔人群中2型糖尿病的基因型危险因素。
