转录因子7-Like-2 (TCF7L2) rs7903146 (C/T)多态性研究

A. Bahaaeldin, A. Seif, A. Hamed, W. Kabiel
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引用次数: 5

摘要

2型糖尿病(T2DM)是一种代谢性疾病,其特征是胰腺不能增加胰岛素分泌来补偿周围组织的胰岛素抵抗。2型糖尿病是一种多因素疾病,包括多种环境因素和遗传易感性。转录因子7-样2基因(TCF7L2) rs7903146 (C/T)多态性是迄今为止发现的T2DM最易感基因之一,通过影响胰岛发育的Wnt/β-catenin信号通路、参与胰岛素颗粒胞吐的几个基因的表达和胰高血糖素样肽1 (GLP-1)基因对T2DM的发病有贡献。然后,TCF7L2基因似乎通过b细胞功能障碍影响糖尿病易感性,这就是为什么我们特别研究了它与T2DM的关系。目的:探讨转录因子7-like-2 (TCF7L2) rs7903146 (C/T)基因多态性与T2DM患者的潜在关联。方法:从艾因沙姆斯大学附属医院内分泌科门诊招募T2DM患者70例,与患者年龄、性别相匹配的非糖尿病健康对照30例进行病例对照研究。所有受试者都进行了完整的病史记录;彻底的临床检查;常规实验室检查包括血红蛋白A1c、总胆固醇、甘油三酯、高密度脂蛋白-胆固醇和低密度脂蛋白-胆固醇;qRT-PCR检测TCF7L2基因多态性。结果:rs7903146(C/T) SNP的次要T等位基因与T2DM的高风险相关,OR为1.35 (95% CI: 0.68-2.6),杂合基因型(CT)与OR为1.16 (95% CI: 0.49-2.7);但差异均无统计学意义(p值>0.05)。结论:本研究未证实TCF7L2 rs7903146(C/T)多态性与T2DM存在显著关联;然而,它指出了TT基因型患者发展为T2DM的高风险存在的可能性。需要更多样本量的进一步研究来阐明这种关联。
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Transcription Factor 7-Like-2 (TCF7L2) rs7903146 (C/T) Polymorphism in Patients with Type 2 Diabetes Mellitus
Introduction: Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by the incapability of pancreas to increase insulin secretion to compensate for insulin resistance in the peripheral tissues. T2DM is a multifactorial disease including several environmental factors with the presence of genetic predisposition. The transcription factor 7-like-2 gene (TCF7L2) rs7903146 (C/T) polymorphism is one of the most susceptible genes to T2DM discovered to date, with contribution to the disease through the Wnt/β-catenin signaling pathway affecting pancreatic islet development, expression of several genes involved in insulin granules exocytosis, and the incretin glucagon-like peptide 1 (GLP-1) gene. Then, TCF7L2 gene seems to affect diabetes susceptibility through B-cell dysfunction that is why we studied its association with T2DM in particular. Objectives: To investigate the potential association of the transcription factor 7-like-2 (TCF7L2) rs7903146 (C/T) gene polymorphism in patients with T2DM. Methods: A case-control study conducted on 70 T2DM patients recruited from the endocrinology clinic at Ain Shams University Hospitals, and 30 non-diabetic healthy controls age- and sex-matched with the patients. All subjects underwent full history taking; thorough clinical examination; routine laboratory investigations including hemoglobin A1c, total cholesterol, triglycerides, high-density lipoprotein-cholesterol, and low-density lipoprotein-cholesterol; and determination of TCF7L2 gene polymorphism by qRT-PCR. Results: The minor T allele of the rs7903146(C/T) SNP was associated with high risk of development of T2DM with an OR of 1.35 (95% CI: 0.68–2.6) and the heterozygous genotype (CT) with an OR 1.16 (95% CI: 0.49–2.7); however, they were statistically insignificant (p value >0.05). Conclusion: Our study did not confirm the presence of significant association between the TCF7L2 rs7903146(C/T) polymorphism and T2DM; however, it pointed out the possibility of presence of high risk of development of T2DM in patients with TT genotype. Further studies with higher sample size are needed to clarify the association.
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