Genetic Determinants of Cellular Homeostasis Contributing to the Risk of Type 2 Diabetes.

IF 1.5 4区生物学 Q4 CELL BIOLOGY

Acta Naturae Pub Date : 2026-04-01 DOI:10.32607/actanaturae.27855

Y R Timasheva, O V Kochetova, T R Nasibullin, T M Kochetova, Z Balkhiyarova, G F Korytina, A Nouwen

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引用次数: 0

Abstract

Genetic variation in the genes involved in the maintenance of cellular homeostasis may influence susceptibility to type 2 diabetes (T2D). However, the nature of the interplay among these loci and their prognostic value remains unclear. In this study, we analyzed variants in the FOXO3A, FOXO3, FOXO1, HMOX1, and SIRT1 genes. The HMOX1 rs2071746*T/T genotype was associated with an increased risk of T2D (OR = 1.36, PFDR = 0.030), whereas the FOXO1 rs9549240 (OR = 0.52, PFDR = 0.002) and SIRT1 rs3758391 (OR = 0.80, PFDR = 0.015) genotypes exhibited a protective effect. We detected nonlinear interactions, including FOXO1 rs9549240*G + SIRT1 rs3758391*T + SIRT1 rs7895833*A and HMOX1 rs2071746*A + SIRT1 rs3758391*T + SIRT1 rs7895833*A, with significant synergistic effects (SF = 3.19 and 2.56, P < 0.03). Models incorporating these interactions achieved an AUC of 69.8%, which increased to 86.2% when combined with age, sex, and the body mass index. These findings suggest that interactions between the pathways regulating oxidative stress and metabolism may contribute to the genetic predisposition to T2D.

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细胞内稳态与2型糖尿病风险相关的遗传决定因素

参与维持细胞内稳态的基因的遗传变异可能影响2型糖尿病（T2D）的易感性。然而，这些基因座之间相互作用的性质及其预后价值仍不清楚。在这项研究中，我们分析了FOXO3A、FOXO3、FOXO1、HMOX1和SIRT1基因的变异。HMOX1 rs2071746*T/T基因型与T2D风险增加相关（OR = 1.36, PFDR = 0.030），而FOXO1 rs9549240 （OR = 0.52, PFDR = 0.002）和SIRT1 rs3758391 （OR = 0.80, PFDR = 0.015）基因型具有保护作用。我们发现FOXO1 rs9549240*G + SIRT1 rs3758391*T + SIRT1 rs7895833*A和HMOX1 rs2071746*A + SIRT1 rs3758391*T + SIRT1 rs7895833*A的非线性相互作用具有显著的协同效应（SF = 3.19和2.56,P < 0.03）。纳入这些相互作用的模型获得了69.8%的AUC，当结合年龄、性别和体重指数时，AUC增加到86.2%。这些发现表明，调节氧化应激和代谢的途径之间的相互作用可能有助于T2D的遗传易感性。

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

Acta Naturae 农林科学-林学

CiteScore

3.50

自引率

5.00%

发文量

审稿时长

>12 weeks

期刊介绍： Acta Naturae is an international journal on life sciences based in Moscow, Russia. Our goal is to present scientific work and discovery in molecular biology, biochemistry, biomedical disciplines and biotechnology. These fields represent the most important priorities for the research and engineering development both in Russia and worldwide. Acta Naturae is also a periodical for those who are curious in various aspects of biotechnological business, innovations in pharmaceutical areas, intellectual property protection and social consequences of scientific progress. The journal publishes analytical industrial surveys focused on the development of different spheres of modern life science and technology. Being a radically new and totally unique journal in Russia, Acta Naturae is useful to both representatives of fundamental research and experts in applied sciences.