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内皮型一氧化氮合酶 (eNOS) 和去甲肾上腺素转运体 (NET) 基因多态性与 2 型糖尿病的关系。

Association of endothelial nitric oxide synthase (eNOS) and norepinephrine transporter (NET) genes polymorphism with type 2 diabetes mellitus.

机构信息

Molecular Biology Lab, Department of Biochemistry, Era's Lucknow Medical College and Hospital, Lucknow, Uttar Pradesh, 226003, India.

Amity University, Lucknow Campus, Lucknow, India.

出版信息

Mol Biol Rep. 2019 Oct;46(5):5433-5441. doi: 10.1007/s11033-019-04998-y. Epub 2019 Aug 3.

DOI:10.1007/s11033-019-04998-y
PMID:31377977
Abstract

Genetic factors in combination with environmental factors play a critical role in the development type 2 diabetes mellitus (T2DM) which is growing as an epidemic globally. In present study we aim to assess the association of eNOS (G894T, rs1799983) and NET (G1287A, rs5569) genes polymorphism with T2DM. A case-control study including a total of 400 North Indian subjects (200 T2DM cases and 200 controls) was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach to analyze genetic polymorphism. Alleles/genotype frequencies between cases and controls were compared using χ and Student's t-tests. Odds ratios and 95% confidence intervals were calculated by logistic regression to assess the relative association between disease and genotypes. In case of NET gene, GG (P = 0.002 in T2DM males, 0.053 in overall T2DM cases) genotype and G allele (P = 0.003 in T2DM males, 0.027 in overall T2DM cases) were found to be a positive risk factors and AG genotype (P = 0.012 in T2DM males) and A allele (P = 0.003 in T2DM males, P = 0.027 in overall T2DM cases) as negative risk factor for T2DM. No association of eNOS gene polymorphism was found with T2DM (P values of all genotypes and alleles were greater than 0.05). NET gene polymorphism might be associated with the risk of T2DM whereas; eNOS gene polymorphism do not confer any risk of T2DM in North Indian Ethnic group. It is hoped that understanding genetic causes of T2DM will lead to earlier diagnosis, preventive measures and more effective and specific treatment.

摘要

遗传因素与环境因素相结合在 2 型糖尿病(T2DM)的发展中起着关键作用,这种疾病在全球范围内呈流行趋势。本研究旨在评估内皮型一氧化氮合酶(eNOS)(G894T,rs1799983)和内皮素(NET)(G1287A,rs5569)基因多态性与 T2DM 的关系。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法对 400 名北印度受试者(200 例 T2DM 病例和 200 例对照)进行了病例对照研究,以分析遗传多态性。使用 χ 和学生 t 检验比较病例组和对照组的等位基因/基因型频率。使用 logistic 回归计算比值比和 95%置信区间,以评估疾病与基因型之间的相对关联。在 NET 基因方面,GG 基因型(男性 T2DM 中 P=0.002,总体 T2DM 中 P=0.053)和 G 等位基因(男性 T2DM 中 P=0.003,总体 T2DM 中 P=0.027)被认为是阳性危险因素,而 AG 基因型(男性 T2DM 中 P=0.012)和 A 等位基因(男性 T2DM 中 P=0.003,总体 T2DM 中 P=0.027)则是阴性危险因素。未发现 eNOS 基因多态性与 T2DM 相关(所有基因型和等位基因的 P 值均大于 0.05)。NET 基因多态性可能与 T2DM 的风险相关,而 eNOS 基因多态性在北印度族群中不会增加 T2DM 的风险。希望对 T2DM 的遗传原因的理解将导致更早的诊断、预防措施和更有效和更具体的治疗。

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本文引用的文献

1
A polymorphism in the norepinephrine transporter gene is associated with affective and cardiovascular disease through a microRNA mechanism.去甲肾上腺素转运体基因的多态性通过 microRNA 机制与情感和心血管疾病相关。
Mol Psychiatry. 2017 Jan;22(1):134-141. doi: 10.1038/mp.2016.40. Epub 2016 Apr 5.
2
Endothelial nitric oxide synthase (eNOS) Glu298-->Asp polymorphism (G894T) among south Indians.印度南部人群中内皮型一氧化氮合酶(eNOS)Glu298→Asp多态性(G894T)
Indian J Med Res. 2009 Jan;129(1):68-71.
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Prevalence of eNOS Glu298Asp polymorphism in healthy volunteers from a region of Northern India.
印度北部某地区健康志愿者中内皮型一氧化氮合酶Glu298Asp多态性的患病率。
Community Genet. 2005;8(3):180-3. doi: 10.1159/000086761.
4
[The G894T mutation of the endothelial nitric oxide synthase gene is associated with coronary atherosclerotic heart disease in Chinese].[内皮型一氧化氮合酶基因G894T突变与中国人群冠状动脉粥样硬化性心脏病的相关性]
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2002 Dec;19(6):471-4.