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Polymorphisms of the Gene Encoding Cytochrome b-245 Beta Chain of NADPH Oxidase: Relationship with Redox Homeostasis Markers and Risk of Type 2 Diabetes Mellitus

  • HUMAN GENETICS
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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.

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Funding

The study was financially supported by the Federal State Budget Educational Institution of Higher Education “Kursk State Medical University” of the Ministry of Health of Russia.

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Authors and Affiliations

  1. Kursk State Medical University, 305041, Kursk, Russia

    I. E. Azarova, E. Yu. Klyosova, I. I. Kolomoets, V. E. Ivakin, A. I. Konoplya & A. V. Polonikov

  2. Kursk Emergency Hospital, 305016, Kursk, Russia

    V. A. Azarova & V. E. Ivakin

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  1. I. E. Azarova
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  2. E. Yu. Klyosova
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  3. I. I. Kolomoets
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Correspondence to I. E. Azarova.

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Statement of compliance with standards of research involving humans as subjects. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants involved in the study.

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Azarova, I.E., Klyosova, E.Y., Kolomoets, I.I. et al. Polymorphisms of the Gene Encoding Cytochrome b-245 Beta Chain of NADPH Oxidase: Relationship with Redox Homeostasis Markers and Risk of Type 2 Diabetes Mellitus. Russ J Genet 56, 856–862 (2020). https://doi.org/10.1134/S1022795420070017

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