Publication date: 2023

DOI: 10.1134/S1022795423020047

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 has been 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 the inflammatory genes FASLG (rs763110), IL19 (rs2243193), IL20 (rs2981573), IL24 (rs291107), PPBP (rs352010), IL4 (rs2243250), IL4 (rs2070874), С5 (rs17611), FAS (rs1800682), IL4RA (rs1805010), and TGFb1 (rs1800469) were 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 an 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; the A allele of IL19 (rs2243193) and C allele of PPBP (rs352010) were the core elements 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: the A allele of IL19 (rs2243193) and AA genotype of IL20 (rs2981573) combination, IL19 (rs2243193), IL12A (rs2243115), PPBP (rs352010), and IL4 (rs2070874) together with age and smoking pack/years, indicating a high ability of the model to correctly classify individuals with and without COPD. © 2023, Pleiades Publishing, Inc.

Издатель: Pleiades Publishing

Тип: Article