| Objective:The purpose of this study was to explore the correlation between the single nucleotide polymorphisms(SNPs)in IL18R1 and the risk of chronic obstructive pulmonary disease(COPD)in Hainan Han population.Methods:This study recruited 498 patients with COPD and 498 controls from Hainan General Hospital.Genotyping of all SNPs were completed by the Agena MassARRAY.PLINK software was used to calculate odds ratio(ORs)and 95%confidence interval(CI)through logistic regression after adjusting for confounding factors to evaluate the association between IL18R1 polymorphisms and risk of COPD under multiple genetic models.Haploview and SNPstats software were used to evaluate linkage disequilibrium between the SNPs and the association between IL18R1 haplotypes and risk of COPD.The interaction of SNP-SNP in COPD risk was evaluated by multi-factor dimensionality reduction(MDR).Finally,the protein interaction network and pathway enrichment analysis of IL18R1 were constructed using String and Sangerbox databases.Results:1.IL18R1 polymorphisms rs9807989(OR=0.42,p=2.38E-06),rs3771166(OR=0.40,p=3.19E-07)and rs6543124(OR=0.44,p=4.35E-05)were significantly associated with reducing the risk of COPD,while rs2287037(OR=2.71,p=9.16E-26)and rs2058622(OR=2.06,p=4.45E-14)were significantly associated with increasing the risk of COPD.2.The haplotype "TTGGT"(OR=2.54,p<0.0001)was significantly associated with increased risk of COPD;while haplotype"CCGAT"(OR=0.41,p=0.036)was significantly associated with reducing the risk of COPD.3.The two loci model(rs2058622 and s3771166)had the highest test accuracy(0.657)and the highest cross validation consistency(10/10),which could be considered as the best model.4.IL-18R1 may be involved in the regulation of related inflammatory pathways or TNF signaling pathways.Conclusion:This study suggests that the IL18R1 polymorphisms rs9807989,rs3771166 and rs6543124 are protective factors for COPD,whereas rs2287037 and rs2058622 are risk factors for COPD. |
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