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GSTM1/GSTT1 多态性对南印度人群 2 型糖尿病患者心血管疾病风险的预测作用。

Progonostic effect of GSTM1/GSTT1 polymorphism in determining cardiovascular diseases risk among type 2 diabetes patients in South Indian population.

机构信息

Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam, Chengalpattu Dt., TN, 603103, India.

出版信息

Mol Biol Rep. 2023 Aug;50(8):6415-6423. doi: 10.1007/s11033-023-08514-1. Epub 2023 Jun 16.

DOI:10.1007/s11033-023-08514-1
PMID:37326751
Abstract

BACKGROUND

Cardiovascular disease (CVD) is a significant complication of type 2 diabetes mellitus (T2DM), with oxidative stress playing a significant role. Glutathione S-transferase (GST) polymorphisms - GSTM1, GSTT1 - have been linked to CVD and T2DM. The role of GSTM1 and GSTT1 in CVD development among T2DM patients in the South Indian population is investigated in this study.

MATERIALS AND METHODS

The volunteers were grouped as Group 1: control, Group 2: T2DM, Group 3: CVD, and Group 4: T2DM with CVD (n = 100 each). Blood glucose, lipid profile, plasma GST, MDA, and total antioxidants were measured. GSTM1 and GSTT1 were genotyped using PCR.

RESULTS

GSTT1 plays a significant role in the development of T2DM and CVD [OR 2.96(1.64-5.33), < 0.001 and 3.05(1.67-5.58), < 0.001] while GSTM1 null genotype was not associated with disease development. Individuals with dual null GSTM1/GSTT1 genotype had the highest risk of developing CVD [3.70(1.50-9.11), 0.004]. Group 2 and 3 individuals showed higher lipid peroxidation and lower total antioxidant levels. Pathway analysis further indicated that GSTT1 significantly affects GST plasma levels.

CONCLUSION

GSTT1 null genotype may be considered a contributing factor that increases the susceptibility and risk of CVD and T2DM in the South Indian population.

摘要

背景

心血管疾病(CVD)是 2 型糖尿病(T2DM)的重要并发症,氧化应激起着重要作用。谷胱甘肽 S-转移酶(GST)多态性-GSTM1、GSTT1-与 CVD 和 T2DM 有关。本研究旨在探讨 GSTM1 和 GSTT1 在南印度人群 T2DM 患者 CVD 发病中的作用。

材料和方法

志愿者分为四组:第 1 组:对照组,第 2 组:T2DM 组,第 3 组:CVD 组,第 4 组:T2DM 合并 CVD 组(每组 100 人)。测量血糖、血脂谱、血浆 GST、MDA 和总抗氧化剂。使用 PCR 对 GSTM1 和 GSTT1 进行基因分型。

结果

GSTT1 在 T2DM 和 CVD 的发展中起重要作用[OR 2.96(1.64-5.33),<0.001 和 3.05(1.67-5.58),<0.001],而 GSTM1 缺失基因型与疾病发展无关。具有双重缺失 GSTM1/GSTT1 基因型的个体发生 CVD 的风险最高[3.70(1.50-9.11),0.004]。第 2 组和第 3 组个体的脂质过氧化作用较高,总抗氧化水平较低。通路分析进一步表明,GSTT1 显著影响 GST 血浆水平。

结论

GSTT1 缺失基因型可能被认为是增加南印度人群 CVD 和 T2DM 易感性和风险的一个因素。

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Molecular Genetics of Abnormal Redox Homeostasis in Type 2 Diabetes Mellitus.2 型糖尿病中异常氧化还原稳态的分子遗传学。
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谷胱甘肽 S-转移酶多态性对 2 型糖尿病患者 CVD 发展的易感性——综述。
Endocr Metab Immune Disord Drug Targets. 2022;22(2):225-234. doi: 10.2174/1871530321666210908115222.
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null polymorphisms may affect the risk of coronary artery disease: evidence from a meta-analysis.无效多态性可能影响冠状动脉疾病风险:一项荟萃分析的证据。
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