Association of CRP , CD14, Pro-Inflammatory Cytokines and Their Receptors ( TNFA , LTA , TNFRSF1A , TNFRSF1B , IL1B , an
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N GENETICS
Association of CRP, CD14, Pro-Inflammatory Cytokines and Their Receptors (TNFA, LTA, TNFRSF1A, TNFRSF1B, IL1B, and IL6) Genes with Chronic Obstructive Pulmonary Disease Development G. F. Korytinaa, b, *, L. Z. Akhmadishinaa, O. V. Kochetovaa, Y. G. Aznabaevab, S. M. Izmailovab, Sh. Z. Zagidullinb, and T. V. Victorovab a Institute
of Biochemistry and Genetics, Subdivision of the Ufa Federal Research Centre of the Russian Academy of Sciences, Ufa, 450054 Russia b Bashkortostan State Medical University, Ufa, 450000 Russia *e-mail: [email protected]
Received September 20, 2019; revised November 20, 2019; accepted December 12, 2019
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). Keywords: chronic obstructive pulmonary disease (COPD), tumor necrosis factor, pro-inflammatory cytokines, C-reactive protein, CD14 DOI: 10.1134/S1022795420080086
INTRODUCTION Chronic obstructive pulmonary disease (COPD) is a multifactorial chronic inflammatory disease of the respiratory system. COPD is characterized by the development of systemic effects leading to severe complications, further worsening the course of the disease [1]. One of the reasons for difficulties in identifying COPD markers is phenotypic heterogeneity. A certain proportion of patients with COPD are more prone to the development of frequent exacerbations of the disease, which cause a sharp progression of airway obstruction and an unfavorable outcome of the disease [2]. Owing to a change in the strategy for the diagnosis and prevention of COPD in 2017, researchers are currently focusing on identifying biomarkers of various phenotypes of the dis
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