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Association of the Aldosterone Synthase Gene (CYP11B2) Polymorphic Locus rs1799998, c.–344C>T with the Development of Pulmonary Sarcoidosis

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Abstract

Pulmonary sarcoidosis is an immunoinflammatory disease. Aldosterone is able to activate cells of the innate immunity, and its level depends on the aldosterone synthase (CYP11B2) activity. The role of the CYP11B2 gene in the etiology and pathogenesis of pulmonary sarcoidosis has not been studied. In this paper, the association of the CYP11B2 gene polymorphism (rs1799998, c.–344T>C) with the development of pulmonary sarcoidosis and the assessment of the relationship between the CYP11B2 gene polymorphic variants and biochemical blood plasma parameters (CRP, VCAM1, IL1, IL6, TNF) were studied. The study included 255 persons (119 patients diagnosed with pulmonary sarcoidosis and 136 healthy donors) living in the Republic of Karelia. Analysis of the rs1799998 locus of the CYP11B2 gene in the indicated groups was carried out by polymerase chain reaction with subsequent restriction fragment length polymorphism analysis (PCR-RFLP). The content of CRP, VCAM1, IL1, IL6, and TNF in the blood plasma of healthy persons was determined by enzyme-linked immunosorbent assay (ELISA). It was found that the frequency of the TT genotype for rs1799998 of the CYP11B2 gene was significantly higher in the group of patients with pulmonary sarcoidosis than in the group of healthy persons (χ2 = 4.05; p = 0.045). An increased risk of developing pulmonary sarcoidosis was revealed in carriers of the T allele (OR = 1.60; 95% CI: 1.102–2.221) and the TT genotype (OR = 2.16; 95% CI: 1.181–3.947). The VCAM1 content in the blood plasma of healthy donors is significantly higher in persons with the TT genotype compared with carriers of alternative genotypes (1465.91 and 967.05 ng/mL, respectively; p = 0.002).

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Funding

This work was financially supported by funds from the federal budget for the implementation of the State Task of the Karelian Research Center of the Russian Academy of Sciences (topic no. 0218-2019-0077).

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Authors and Affiliations

  1. Institute of Biology, Karelian Research Center, Russian Academy of Sciences, 185910, Petrozavodsk, Russia

    I. E. Malysheva & L. V. Topchieva

  2. Baranov Republican Hospital, 185019, Petrozavodsk, Russia

    E. L. Tikhonovich

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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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Malysheva, I.E., Topchieva, L.V. & Tikhonovich, E.L. Association of the Aldosterone Synthase Gene (CYP11B2) Polymorphic Locus rs1799998, c.–344C>T with the Development of Pulmonary Sarcoidosis. Russ J Genet 57, 591–597 (2021). https://doi.org/10.1134/S1022795421040074

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