NADPH oxidase 5 is a novel susceptibility gene for type 2 diabetes mellitus.

IF 1.6 4区医学 Q4 ENDOCRINOLOGY & METABOLISM

Archives of Endocrinology Metabolism Pub Date : 2024-10-17 eCollection Date: 2024-01-01 DOI:10.20945/2359-4292-2023-0527

Iuliia Azarova, Elena Klyosova, Valentina Azarova, Alexey Polonikov

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引用次数: 0

Abstract

Objective: This pilot study investigated whether single nucleotide polymorphisms (SNP) in the NOX5 gene (NADPH oxidase 5) are associated with the type 2 diabetes (T2D) risk.

Subjects and methods: A total of 1579 patients with T2D and 1627 age- and sex-matched healthy subjects were recruited for this study. Genotyping of common SNPs, namely rs35672233, rs3743093, rs2036343, rs311886, and rs438866, was performed using the MassArray-4 system.

Results: SNP rs35672233 was associated with an increased risk of T2D (OR = 1.67, 95% CI 1.29-2.17, FDR = 0.003). The H3 haplotype (rs35672233T-rs3743093G-rs2036343A-rs311886C-rs438866C) increased T2D risk (OR = 1.65, 95% CI 1.27-2.13, FDR = 0.001). The rs35672233 polymorphism and H3 haplotype were found to have an association with T2D risk only in subjects with a body mass index greater than 25 kg/m² (FDR < 0.01). Environmental risk factors, such as chronic psycho-emotional stress, sedentary lifestyle, high-calorie diet and SNP rs35672233 were jointly associated with T2D susceptibility. A haplotype comprising the allele rs35672233-C and conferring protection against T2D, was associated with elevated levels of antioxidants such as total glutathione and uric acid, as well as reduced levels of two-hour postprandial glucose in the plasma of patients. The NOX5 polymorphisms showed no associations with diabetic complications.

Conclusion: The present study is the first to establish associations between polymorphisms in NOX5 and the risk of type 2 diabetes mellitus, and provides a new line of evidence for the crucial role of oxidative stress-related genes in disease susceptibility.

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NADPH 氧化酶 5 是 2 型糖尿病的新型易感基因。

研究目的这项试验性研究探讨了 NOX5 基因（NADPH 氧化酶 5）中的单核苷酸多态性（SNP）是否与 2 型糖尿病（T2D）风险有关：本研究共招募了 1579 名 T2D 患者和 1627 名年龄与性别匹配的健康受试者。使用 MassArray-4 系统对常见 SNPs（即 rs35672233、rs3743093、rs2036343、rs311886 和 rs438866）进行基因分型：结果：SNP rs35672233 与 T2D 风险增加有关（OR = 1.67，95% CI 1.29-2.17，FDR = 0.003）。H3 单倍型（rs35672233T-rs3743093G-rs2036343A-rs311886C-rs438866C）增加了 T2D 风险（OR = 1.65，95% CI 1.27-2.13，FDR = 0.001）。只有体重指数大于 25 kg/m2 的受试者的 rs35672233 多态性和 H3 单倍型才与 T2D 风险有关（FDR < 0.01）。环境风险因素，如长期心理情绪压力、久坐不动的生活方式、高热量饮食和 SNP rs35672233 与 T2D 易感性共同相关。由等位基因 rs35672233-C 组成的单倍型具有预防 T2D 的作用，它与患者血浆中谷胱甘肽和尿酸等抗氧化剂水平的升高以及餐后两小时血糖水平的降低有关。NOX5 多态性与糖尿病并发症没有关联：本研究首次确定了 NOX5 多态性与 2 型糖尿病风险之间的关系，为氧化应激相关基因在疾病易感性中的关键作用提供了新的证据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Archives of Endocrinology Metabolism Medicine-Endocrinology, Diabetes and Metabolism

CiteScore

2.90

自引率

5.90%

发文量

107

审稿时长

7 weeks

期刊介绍： The Archives of Endocrinology and Metabolism - AE&M – is the official journal of the Brazilian Society of Endocrinology and Metabolism - SBEM, which is affiliated with the Brazilian Medical Association. Edited since 1951, the AE&M aims at publishing articles on scientific themes in the basic translational and clinical area of Endocrinology and Metabolism. The printed version AE&M is published in 6 issues/year. The full electronic issue is open access in the SciELO - Scientific Electronic Library Online e at the AE&M site: www.aem-sbem.com. From volume 59 on, the name was changed to Archives of Endocrinology and Metabolism, and it became mandatory for manuscripts to be submitted in English for the online issue. However, for the printed issue it is still optional for the articles to be sent in English or Portuguese. The journal is published six times a year, with one issue every two months.