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Association of CRP, CD14, Pro-Inflammatory Cytokines and Their Receptors (TNFA, LTA, TNFRSF1A, TNFRSF1B, IL1B, and IL6) Genes with Chronic Obstructive Pulmonary Disease Development

  • HUMAN GENETICS
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Abstract

The aim of the present study was to investigate the association of COPD and frequent exacerbator COPD phenotype with CRP, CD14, and pro-inflammatory cytokines and their receptors (TNFA, LTA, TNFRSF1A, TNFRSF1B, IL1B, and IL6) genes. It was found that COPD was associated with allele A of the TNFA gene (rs1800629G>A) (P = 0.002, OR = 1.45); the association was established in the log-additive model (P = 0.0022, Pcor-FDR = 0.01705, OR = 1.47); this association was confirmed in the frequent exacerbator COPD phenotype group (P = 0.001, Pcor-FDR = 0.007, OR = 1.59). Allele G of the LTA gene (rs909253A>G) (P = 0.002, OR = 1.33) was also shown to be a marker for COPD risk; the association was established in the log-additive model (P = 0.0021, Pcor-FDR = 0.01705, OR = 1.31) and it was confirmed in patients with rare exacerbations (P = 0.003, Pcor-FDR = 0.0084, OR = 1.39). The genotype GG of the TNFRSF1B gene (rs1061622T>G) was a marker of resistance to the development of the frequent exacerbator COPD phenotype (P = 0.003, Pcor-FDR = 0.0084, OR = 0.46). The genotype CC of the CD14 gene (rs2569190T>C) was associated with higher forced expiratory volume in 1 s (P = 0.006); subjects with genotype AA of the TNFRSF1B gene (rs1061624A >G) and genotype GG of the LTA gene (rs909253A>G) exhibited lower forced expiratory volume in 1 s (P = 0.04 and P = 0.01, respectively). Genotype AA of the TNFRSF1A gene (rs767455A>G) was associated with higher smoking pack-years (P = 0.0036).

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Funding

This work was partially supported by the Russian Foundation for Basic Research (project no. 18-015-00050) and the research work no. АААА-А16-116020350031-4; biological material (DNA) for research was taken from the collection of human biological materials of the Institute of Biochemistry and Genetics, Ufa Scientific Centre, Russian Academy of Sciences, supported by the program of bioresource collections of the Federal Agency for Scientific Organizations of Russia; the work was performed using the equipment of the Centre for Collective Use Biomika and the unique KODINK research facility (Institute of Biochemistry and Genetics, Ufa Federal Research Centre, Russian Academy of Sciences).

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  1. Institute of Biochemistry and Genetics, Subdivision of the Ufa Federal Research Centre of the Russian Academy of Sciences, 450054, Ufa, Russia

    G. F. Korytina, L. Z. Akhmadishina & O. V. Kochetova

  2. Bashkortostan State Medical University, 450000, Ufa, Russia

    G. F. Korytina, Y. G. Aznabaeva, S. M. Izmailova, Sh. Z. Zagidullin & T. V. Victorova

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  1. G. F. Korytina
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  2. L. Z. Akhmadishina
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Correspondence to G. F. Korytina.

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Statement of compliance with standards of research involving humans as subjects. All procedures carried out in a study with the participation of people comply with the ethical standards of the institutional and/or national research ethics committee and the 1964 Helsinki Declaration and its subsequent changes or comparable standards of ethics. Informed voluntary consent was obtained from each of the participants in the study.

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Translated by A. Kashevarova

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Korytina, G.F., Akhmadishina, L.Z., Kochetova, O.V. et al. Association of CRP, CD14, Pro-Inflammatory Cytokines and Their Receptors (TNFA, LTA, TNFRSF1A, TNFRSF1B, IL1B, and IL6) Genes with Chronic Obstructive Pulmonary Disease Development. Russ J Genet 56, 972–981 (2020). https://doi.org/10.1134/S1022795420080086

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