The Relationship Between Chemokine and Chemokine Receptor Genes Polymorphisms and Chronic Obstructive Pulmonary Disease Susceptibility in Tatar Population from Russia: A Case Control Study
Autor: | Viktorova Tv, Naufal Sh. Zagidullin, Shamil Zagidullin, Timur R. Nasibullin, L. Z. Akhmadishina, O. V. Kochetova, Gulnaz F. Korytina, Yulia G. Aznabaeva |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
medicine.medical_specialty Vital capacity CCR2 Population Single-nucleotide polymorphism C-C chemokine receptor type 6 Biology Biochemistry CCL8 Gastroenterology 03 medical and health sciences 0302 clinical medicine Internal medicine Genetic model Genetics medicine education Molecular Biology Ecology Evolution Behavior and Systematics education.field_of_study COPD hemic and immune systems General Medicine medicine.disease respiratory tract diseases 030104 developmental biology 030220 oncology & carcinogenesis |
Zdroj: | Biochemical Genetics. 60:54-79 |
ISSN: | 1573-4927 0006-2928 |
Popis: | 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 |
Databáze: | OpenAIRE |
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