Abstract
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease affecting primarily distal respiratory pathways and lung parenchyma. This study aimed to determine possible genetic association of chemokine and chemokine receptor genes polymorphisms with COPD in a Tatar population from Russia. SNPs of CCL20, CCR6, CXCL8, CXCR1, CXCR2, CCL8, CCL23, CCR2, and CX3CL1 genes and their gene–gene interactions were analyzed for association with COPD in cohort of 601 patients and 617 controls. As a result statistically significant associations with COPD in the study group under the biologically plausible assumption of additive genetic model were identified in CCL20 (rs6749704) (P = 0.00001, OR 1.55), CCR6 (rs3093024) (P = 0.0003, OR 0.74), CCL8 (rs3138035) (P = 0.0001, OR 0.67), CX3CL1 (rs170364) (P = 0.023, OR 1.21), CXCL8 (rs4073) (P = 0.007, OR 1.23), CXCR2 (rs2230054) (P = 0.0002, OR 1.32). Following SNPs CCL20 (rs6749704), CX3CL1 (rs170364), CCL8 (rs3138035), CXCL8 (rs4073), CXCR2 (rs2230054) showed statistically significant association with COPD only in smokers. The association of CCR6 (rs3093024) with COPD was confirmed both in smokers and in non-smokers. A relationship between smoking index and CCL20 (rs6749704) (P = 0.04), CCR6 (rs3093024) (P = 0.007), CCL8 (rs3138035) (P = 0.0043), and CX3CL1 (rs170364) (P = 0.04) was revealed. A significant genotype-dependent variation of Forced Vital Capacity was observed for CCL23 (rs854655) (P = 0.04). Forced Expiratory Volume in 1 s / Forced Vital Capacity ratio was affected by CCL23 (rs854655) (P = 0.05) and CXCR2 (rs1126579) (P = 0.02). Using the APSampler algorithm, we obtained nine gene–gene combinations that remained significantly associated with COPD; loci CCR2 (rs1799864) and CCL8 (rs3138035) were involved in the largest number of the combinations. Our results indicate that CCL20 (rs6749704), CCR6 (rs3093024), CCR2 (rs1799864), CCL8 (rs3138035), CXCL8 (rs4073), CXCR1 (rs2234671), CXCR2 (rs2230054), and CX3CL1 (rs170364) polymorphisms are strongly associated with COPD in Tatar population from Russia, alone and in combinations. For the first time combination of the corresponding SNPs were considered and as a result 8 SNP patterns were associated with increased risk of COPD
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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
We thank all the COPD patients, healthy volunteers and staff of the pulmonary department of Ufa City Hospitals No.21 (Ufa, Russia). This work was supported by the Russian Foundation for Basic Research Grants (No.18-015-00050), DNA samples for the study are taken from “Collections of human biological materials IBG UFIC RAS” supported by the Federal Agency for Scientific Organizations program for support the bioresource collections (Grant No. 007-030164/2). 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). Partial financial support for research by the Ministry of Higher Education and Science of Russian Federation (Grant No. AAAA-A21-121011990119-1) and Megagrant from the Government of Russian Federation (Grant No. 2020-220-08-2197).
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GK: conceptualization, funding acquisition, writing—original draft, writing—review & editing, methodology, project administration. LA: methodology, validation. YA: methodology, investigation, resources. OK: investigation, validation. TRN: Formal analysis, visualization. NSZ: methodology, formal analysis, visualization. SZZ: supervision, investigation, resources, writing—review & editing. TV: supervision, writing—review & editing. All authors critically commented and approved the manuscript.
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Korytina, G.F., Aznabaeva, Y.G., Akhmadishina, L.Z. et al. The Relationship Between Chemokine and Chemokine Receptor Genes Polymorphisms and Chronic Obstructive Pulmonary Disease Susceptibility in Tatar Population from Russia: A Case Control Study. Biochem Genet 60, 54–79 (2022). https://doi.org/10.1007/s10528-021-10087-2
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DOI: https://doi.org/10.1007/s10528-021-10087-2