Abstract

Chronic obstructive pulmonary disease (COPD) is a complex lung disease characterized by progressive airflow limitation and abnormal inflammatory response of the lungs to inhaled noxious particles or gases. COPD pathogenesis was linked to oxidative stress and systemic inflammation. We aimed to assess the association of cytokines and inflammatory genes polymorphisms and their combinations with COPD. SNPs of inflammatory genes FASLG (rs763110), IL19 (rs2243193), IL20 (rs2981573), IL24 (rs291107), PPBP (rs352010), IL4 (rs2243250), IL4 (rs2070874), С5 (rs17611), FAS (rs1800682), IL4RA (rs1805010), TGFb1 (rs1800469) was genotyped by the real-time polymerase chain reaction (PCR) among 601 COPD patients and 617 controls. Significant associations with COPD in the study group under additive genetic model were identified for IL19 (rs2243193) (P = 0.00001, OR = 0.73), IL4 (rs2243250) (P = 0.024, OR = 1.27), IL4 (rs2070874) (P = 0.00001, OR = 0.62), and for PPBP (rs352010) under the recessive model (P = 0.00001, OR = 2.34). Using the APSampler algorithm, we obtained gene-gene combinations that remained significantly associated with COPD; A allele of IL19 (rs2243193) and C allele of PPBP (rs352010) were the core element of the majority of protective patterns associated with COPD. The highest risk of COPD was conferred by combination of alleles: G of IL12A (rs2243115) with A of IL13 (rs20541) and C of IL4 (rs2070874) (OR = 2.72). The receiver operating characteristic (ROC) analysis resulted in an area under the curve (AUC) of 0.895 (95%CI 0.874–0.916) for model including SNPs: A allele of IL19 (rs2243193) and AA genotype of IL20 (rs2981573) combination, IL19 (rs2243193), IL12A (rs2243115), PPBP (rs352010), IL4 (rs2070874) together with age and smoking pack years, indicating a high ability of the model to correctly classify individuals with and without COPD.

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