- OBJECTIVE: COPD is a complex re-spiratory disease characterized by chronic airway inflammation and the airflow limitations are not ful-ly reversible due to the combination of genetic and environmental factors. Genetic factors such as poly-morphisms, may affect the susceptibility of COPD. In the present study, we examined the association between the polymorphisms of three genes and COPD risk in a Chinese Han population.PATIENTS AND METHODS: A total of 375 COPD patients and 284 control subjects were recruited from November 2018 to June 2021. Data on demo-graphic basic information, smoking status, history of coal dust exposure, and peripheral blood were collected from subjects of two groups. Three poly-morphisms (NLRP3 rs1539019, LAMB1 rs4320486, IL-6 rs1800796) were analyzed. Logistic analysis was used to evaluate the genetic contribution of selected SNPs to COPD susceptibility.RESULTS: The AC genotype of NLRP3 rs1539019 significantly decreased COPD risk compared with CC genotype (adjusted OR = 0.508, 95% CI 0.336-0.767). In the stratification analyses, the AC genotype signifi-cantly decreased the risk of COPD in subjects aged 60 and over (p=0.005; adjusted OR = 0.553; 95% CI 0.366-0.835) with current smoking status (p=0.002; adjusted OR = 0.419; 95% CI 0.240-0.732) when com-pared with AA+CC genotype. Moreover, a significant-ly decreased risk for GOLD III COPD was found in genotype AC of NLRP3 rs1539019 (p=0.006; adjust-ed OR = 0.502; 95% CI 0.306-0.822).CONCLUSIONS: Our present study revealed that the genotype AC of NLRP3 rs1539019 is related to a decreased risk of COPD in a Chinese Han popula-tion, a large-sample, multi-center, multi-ethnic study is needed to further confirm our study.