Abstract

The aim of this study was to investigate the associations of the single-nucleotide polymorphisms (SNPs) rs5917471, rs5963327 and rs6610650 of the gene encoding the beta chain of cytochrome b-245 of NADPH oxidase (CYBB gene) with the redox-homeostasis parameters of blood plasma and the risk of development of type 2 diabetes mellitus (T2D). The study included 2086 unrelated individuals of Slavic origin (1022 patients with T2D and 1064 healthy volunteers). Genotyping of SNPs was performed on a MassArray Analyzer 4 genomic mass spectrometer. Due to the localization of the CYBB gene on the X chromosome, the analysis of the effect of its single nucleotide variants on the predisposition to T2D and the parameters of the redox status of blood plasma was carried out separately in men and women by the method of linear regression analysis, adjusted for age and body mass index. In men, the association of the allele T rs5963327 (OR 1.7, 95% CI 1.06–2.75, P = 0.028) and the allele A rs6610650 (OR 1.71, 95% CI 1.05–2.78, P = 0.029) with an increased risk of T2D development was established. Genotype T/T rs5963327 (OR 1.35, 95% CI 1.05–1.73, P = 0.017) and genotype A/A rs6610650 (OR 1.34, 95% CI 1.05–1.72, P = 0.020) were also associated with the risk of T2D development in women. The T-T-A haplotype, including minor alleles of the studied rs5917471–rs5963327–rs6610650 polymorphisms, was associated with an increased risk of developing T2D in both men (OR 1.29, 95% CI 1.04–1.58, P = 0.022) and women (OR 1.27, 95% CI 1.02–1.58, P = 0.034). Patients with T2D had a significantly higher content of hydrogen peroxide in their plasma compared to the control group (P < 0.05), regardless of sex. However, the relationship between rs5963327 and rs6610650 and an increased content of oxidized glutathione (GSSG) was only found female participants. Thus, for the first time, we detected associations between the rs5963327 and rs6610650 SNPs of the CYBB gene and both the redox status of patients and the development of T2D. The studied polymorphic variants of the gene encoding the beta chain of cytochrome b-245 of NADPH oxidase may contribute to a shift in the balance of the redox homeostasis system towards the prooxidant status, which is characteristic of T2D.

中文翻译：

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NADPH氧化酶细胞色素b-245 Beta链编码基因的多态性：与氧化还原稳态标记和2型糖尿病风险的关系。

摘要

这项研究的目的是调查编码NADPH氧化酶（CYBB基因）的细胞色素b- 245β链的基因的单核苷酸多态性（SNP）rs5917471，rs5963327和rs6610650与氧化还原稳态参数血浆和罹患2型糖尿病（T2D）的风险。该研究包括2086名来自斯拉夫血统的无关个体（1022名T2D患者和1064名健康志愿者）。SNP的基因分型在MassArray Analyzer 4基因组质谱仪上进行。由于CYBB的本地化通过线性回归分析方法，对男性和女性分别进行了X染色体X染色体上的基因，其单核苷酸变异对T2D易感性的影响以及血浆氧化还原状态参数的分析，并根据年龄进行了调整和体重指数。在男性中，等位基因T rs5963327（OR 1.7，95％CI 1.06–2.75，P = 0.028）和等位基因A rs6610650（OR 1.71，95％CI 1.05–2.78，P = 0.029）的相关性增加。建立了T2D开发。基因型T / T rs5963327（OR 1.35，95％CI 1.05-1.73，P = 0.017）和基因型A / Ars6610650（OR 1.34，95％CI 1.05-1.72，P = 0.020）也与女性发生T2D的风险有关。该牛逼-牛逼-一个单倍型，包括研究的rs5917471-rs5963327-rs6610650多态性的次要等位基因，用在男女双方发展T2D的风险增加（OR 1.29，95％CI 1.04-1.58，相关P = 0.022）和女性（或1.27，95％CI 1.02-1.58，P = 0.034）。与对照组相比，患有T2D的患者血浆中的过氧化氢含量明显更高（P<0.05），无论性别。但是，仅女性参与者发现了rs5963327和rs6610650与氧化型谷胱甘肽（GSSG）含量增加之间的关系。因此，我们首次检测到CYBB基因的rs5963327和rs6610650 SNP与患者的氧化还原状态和T2D的发展之间的关联。编码NADPH氧化酶的细胞色素b-245的β链的基因的多态性变异研究可能有助于氧化还原稳态系统的平衡向前氧化状态的转变，这是T2D的特征。