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Am. J. Respir. Crit. Care Med., Volume 165, Number 2, January 2002, 148-151

Interleukin-1 Gene Cluster Polymorphisms in Sarcoidosis and Idiopathic Pulmonary Fibrosis

BEÁTA HUTYROVÁ, PANAGIOTIS PANTELIDIS, JIRÍ DRÁBEK, MONIKA ZŮRKOVÁ, VÍTEZSLAV KOLEK, KAREL LENHART, KENNETH I. WELSH, ROLAND M. DU BOIS, and MARTIN PETREK

Departments of Immunology, Biology, and Respiratory Medicine, PalackýUniversity, Olomouc, Czech Republic; and Molecular Genetics Unit, Imperial College of Science, Technology and Medicine, London, United Kingdom

Members of the interleukin-1 (IL-1) family are implicated in the pathogenesis of sarcoidosis and idiopathic pulmonary fibrosis (IPF). We have, therefore, performed a case-control study to investigate a plausible association between sarcoidosis and the polymorphisms in the IL-1alpha , IL-1beta , and IL-1 receptor antagonist (IL-1Ra) genes. Further, as a separate question, we explored whether the aforementioned genes of the IL-1 cluster are associated with IPF. Using PCR with sequence-specific primers, IL-1alpha -889, IL-1beta -511, IL-1beta +3953, and IL-1Ra intron 2 VNTR polymorphisms were determined in 348 white subjects of West Slavonic ancestry (95 patients with sarcoidosis, 54 patients with IPF, and 199 healthy control subjects). The IL-1alpha -889 1.1 genotype was significantly overrepresented in patients with sarcoidosis in comparison with control subjects (60.0 versus 44.2%, p = 0.012, pcorr = 0.047). The distribution of IL-1beta -511, IL-1beta +3953, and IL-1Ra VNTR genotypes and alleles did not significantly differ between the cases and controls. No association between IPF and the investigated polymorphisms was found. Strong linkage disequilibrium between pairs of polymorphic loci was observed. Further population studies are warranted to confirm the observed association between sarcoidosis and the IL-1alpha polymorphism and also to explore mechanisms of IL-1alpha -889 participation in aberrant immune response in sarcoidosis.




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