Abstract
Chronic obstructive pulmonary disease (COPD) is a complex chronic inflammatory disease of the respiratory system affecting primarily distal respiratory pathways and lung parenchyma. This work was designed as a case–control study aimed at investigating the association of COPD with polymorphisms in inflammatory and immune response genes (JAK1, JAK3, STAT1, STAT3, NFKB1, IL17A, ADIPOQ, ADIPOR1, etc.) in Tatar population from Russia. Ten SNPs (rs310216, rs3212780, rs12693591, rs2293152, rs28362491, rs4711998, rs1974226, rs1501299, rs266729, and rs12733285) were genotyped by the real-time polymerase chain reaction (TaqMan assays) in a case–control study (425 COPD patients and 457 in the control group, from Ufa, Russia). Logistic regression was used to detect the association of SNPs in different models. Linear regression analyses were performed to estimate the relationship between SNPs and lung function parameters and pack-years. In Tatar population, significant associations of JAK1 (rs310216) (P = 0.0002, OR 1.70 in additive model), JAK3 (rs3212780) (P = 0.001, OR 1.61 in dominant model), and IL17A (rs1974226) (P = 0.0037, OR 2.31 in recessive model) with COPD were revealed. The disease risk was higher in carriers of insertion allele of NFKB1 (rs28362491) (P = 0.045, OR 1.22). We found a significant gene-by-environment interaction of smoking status and IL17A (rs1974226) (P interact = 0.016), JAK3 (rs3212780) (P interact = 0.031), ADIPOQ (rs266729) (P interact = 0.013), and ADIPOR1 (rs12733285) (P interact = 0.018). The relationship between the rs4711998, rs1974226, rs310216, rs3212780, rs28362491, and smoking pack-years was found (P = 0.045, P = 0.004, P = 0.0005, P = 0.021, and P = 0.042). A significant genotype-dependent variation of forced vital capacity was observed for NFKB1 (rs28362491) (P = 0.017), ADIPOR1 (rs12733285) (P = 0.043), and STAT1 (rs12693591) (P = 0.048). The genotypes of STAT1 (rs12693591) (P = 0.013) and JAK1 (rs310216) (P = 0.048) were associated with forced expiratory volume in 1 s.
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Acknowledgments
This work was supported by the Russian Foundation for Basic Research Grants (Nos. 13-04-00287, 14-04-97006, and 14-06-97003), and the Russian Foundation for Humanities Grant No. 16-06-00162).
Author Contributions
The conception and study design of the work: G. F. Korytina, T.V. Viktorova, Sh.Z. Zagidullin. The patients and control—medical examination and selection: Y.G. Aznabaeva, Sh.Z. Zagidullin. Performing the experiment (case and control—DNA-collecting; real-time PCR): G. F. Korytina, L. Z. Akhmadishina, O.V. Kochetova. Genetic association analysis: G. F. Korytina, L. Z. Akhmadishina, O.V. Kochetova. Statistical analysis: G. F. Korytina. Interpretation of data for the work: G. F. Korytina, T.V. Viktorova, Z. Akhmadishina, O.V. Kochetova, Y.G. Aznabaeva, Sh.Z. Zagidullin. Manuscript writing: G. F. Korytina, T.V. Viktorova, L. Z. Akhmadishina, Y.G. Aznabaeva, Sh.Z. Zagidullin, O.V. Kochetova. Review of the manuscript: G. F. Korytina, T.V. Viktorova, L. Z. Akhmadishina, Y.G. Aznabaeva, Sh.Z. Zagidullin., O.V. Kochetova.
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Korytina, G.F., Akhmadishina, L.Z., Kochetova, O.V. et al. Inflammatory and Immune Response Genes Polymorphisms are Associated with Susceptibility to Chronic Obstructive Pulmonary Disease in Tatars Population from Russia. Biochem Genet 54, 388–412 (2016). https://doi.org/10.1007/s10528-016-9726-0
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DOI: https://doi.org/10.1007/s10528-016-9726-0