IL18 and IL18R1 polymorphisms, lung HRCT and fibrosis: a longitudinal study in coal miners

¹ INSERM U780, Villejuif, France; and Université Paris Sud, Faculté de médecine, IFR69, Villejuif, France
² Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD USA
³ Laboratory of Respiratory Biology, National Institute of Environmental Health Sciences, Research Triangle Park, NC USA

^* To whom correspondence should be addressed. E-mail: nadif{at}vjf.inserm.fr.

	Abstract

Interleukin (IL)-18 has been suggested to play a role in the development of inflammatory and fibrosing lung diseases.

Associations of polymorphisms in IL18 (G-656T, C-607A, G-137C, T113G, C127T) and its receptor IL18R1 (C-69T) with Coal Workers' Pneumoconiosis (CWP) were studied in 200 miners who were examined in 1990, 1994 and 1999. Coal dust exposure was assessed by job history and ambient measures. The main health outcome was lung computed tomography (CT) score in 1990. Internal coherence was assessed by studying CT score in 1994, 4-year change in CT score and CWP incidence and prevalence.

CT score in 1990 was a good predictor of x ray grade in 1999, and therefore an appropriate subclinical quantitative trait. The IL18 -137 C allele was associated with lower CT score in 1990 and 1994 (1.24 vs. 1.69, p=0.2; 1.57 vs. 2.46, p=0.02), slower progression of CT score between 1990 and 1994 and lower pneumoconiosis prevalence in 1999 relative to the G allele (0.33 vs. 0.77 p = 0.03 and 8.2 vs. 19.6% p=0.02). Smoking or dust-adjustment, stratification on IL18R1 genotype and adjustment for haplotype effects did not change the conclusions.

Results suggest a role for IL18 in reducing the development of this fibrosing lung disease.

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