Polymorphisms in interleukin-1B and its receptor antagonist genes and the risk of chronic obstructive pulmonary disease in a Korean population: a case-control study

Background: Although several studies have evaluated the association between interleukin-1B (IL1B) polymorphisms and the risk of chronic obstructive pulmonary disease (COPD), most of these studies have focused on -511C -> T and -31T -> C polymorphisms, and the results of these studies have been inconsistent. This study was conducted to investigate the association between four potentially functional polymorphisms of the IL1B gene (-3737C -> T, -14646 -> C, -511C -> T, and -31T -> C) and the risk of COPD. In addition, we examined a potential interaction of the IL1B polymorphisms with the VNTR polymorphism of the IL-1 receptor antagonist (IL1RN) gene in determining the risk of COPD. Methods: The IL1B and IL1RN genotypes were determined in 311 COPD patients and 386 healthy controls. Results: Individuals with at least one variant allele of the -511C -> T and -31T -> C polymorphisms were at a significantly increased risk for COPD when compared to carriers with each homozygous wild-type allele [adjusted odds ratio (OR) 1.53, 95% confidence interval (CI) 1.03-2.26, P = 0.03; and adjusted OR 1.50, 95% CI 1.02-2.24, P = 0.04, respectively]. When the COPD cases were stratified according to disease severity, the presence of at least one -511T and -31C alleles was significantly associated with severe COPD (adjusted OR 2.80, 95% CI 1.47-5.33, P = 0.002; and adjusted OR 2.33, 95% CI 1.24-4.40, P = 0.01, respectively), however, there was no significant association between the -511C -> T and -31T -> C genotypes and mild-to-moderate COPD. In addition, individuals carrying at least one IL1RN*2 allele were at a significantly tower risk for COPD compared to subjects carrying no IL1RN*2 allele (adjusted OR 0.51, 95% CI 0.26-0.98, P = 0.04). In haplotype/diptotype analyses, individuals with one or two copies of the IL18 CCTC haplotype that carried the risk allele at all of the -3737C -> T, -14646 -> C, -511C -> T, and -31T -> C loci, were at a significantly increased risk of severe COPD when compared with subjects with zero copy of the CCTC haplotype (adjusted OR 1.96, 95% CI 1.16-3.29, P = 0.01). Conclusion: These findings suggest that polymorphisms in the IL1B and IL1RN genes might be useful markers for determining genetic susceptibility to COPD in a Korean population. (C) 2008 Elsevier Ltd. All rights reserved.