Association ofCRP,CD14,Pro-Inflammatory Cytokines and Their Receptors (TNFA,LTA,TNFRSF1A,TNFRSF1B,IL1B, andIL6) Genes with Chronic Obstructive Pulmonary Disease Development

摘要

The aim of the present study was to investigate the association of COPD and frequent exacerbator COPD phenotype withCRP,CD14, and pro-inflammatory cytokines and their receptors (TNFA,LTA,TNFRSF1A,TNFRSF1B,IL1B, andIL6) genes. It was found that COPD was associated with alleleAof theTNFAgene (rs1800629G>A) (P= 0.002, OR = 1.45); the association was established in the log-additive model (P= 0.0022,Pcor-FDR= 0.01705, OR = 1.47); this association was confirmed in the frequent exacerbator COPD phenotype group (P =0.001,Pcor-FDR= 0.007, OR = 1.59). AlleleGof theLTAgene (rs909253A>G) (P= 0.002, OR = 1.33) was also shown to be a marker for COPD risk; the association was established in the log-additive model (P= 0.0021,Pcor-FDR= 0.01705, OR = 1.31) and it was confirmed in patients with rare exacerbations (P= 0.003,Pcor-FDR= 0.0084, OR = 1.39). The genotypeGGof theTNFRSF1Bgene (rs1061622T>G) was a marker of resistance to the development of the frequent exacerbator COPD phenotype (P =0.003,Pcor-FDR= 0.0084, OR = 0.46). The genotypeCCof theCD14gene (rs2569190T>C) was associated with higher forced expiratory volume in 1 s (P= 0.006); subjects with genotypeAAof theTNFRSF1Bgene (rs1061624A >G) and genotypeGGof theLTAgene (rs909253A>G) exhibited lower forced expiratory volume in 1 s (P= 0.04 andP= 0.01, respectively). GenotypeAAof theTNFRSF1Agene (rs767455A>G) was associated with higher smoking pack-years (P= 0.0036).