Polymorphisms of the IL-1 gene complex in coal miners with silicosis

Background Silicosis is characterized by fibrosing nodular lesions that eve ntually develop into progressive pulmonary fibrosis. Pro-inflammatory cytok ines, such as interleukin-l (IL-I), play a key role in the development of s ilicosis by regulating mediators which are responsible for lung injury, inf lammation, and potentially fibrosis. To study whether functional single nuc leotide polymorphisms (SNPs) located in the regulatory elements of genes co ding for the IL-1 alpha, IL-1 beta, and IL-1 receptor antagonist (RA) cytok ines are associated with silicosis, we examined 318 Caucasian cases confirm ed histopathologically with pulmonary silicosis and 163 controls without an y apparent inflammation or other pulmonary disease. Methods Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism technique. Results The proportion of the IL-IRA ( + 2018) allele 2 genotype was increa sed in miners with silicosis (0.27) compared to controls (0.16). The odds o f being a case were 2.15 (CI=1.4-3.3) times higher for subjects with at lea st one copy of allele 2. No statistically significant differences in the al lelic frequencies or genotype distributions for IL-1 alpha ( + 4845) or IL- 1 beta ( + 3953) were found between the control and disease groups. Conclusions This is the first report showing an association between the IL- IRA (+ 2018) polymorphism and silicosis, and suggests that this polymorphis m may confer increased risk for the development of the disease. Published 2 001 Wiley-Liss, Inc.(dagger)