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Am. J. Respir. Crit. Care Med., Volume 164, Number 2, July 2001, 197-201

ACE Gene I/D Polymorphism and Sarcoidosis Pulmonary Disease Severity

DEIRDRE S. McGRATH, PATRICK J. FOLEY, MARTIN PETREK, LYDIE IZAKOVICOVA-HOLLA, VITEZSLAV DOLEK, SRIHARI VEERARAGHAVAN, PENELOPE A. LYMPANY, PANAGIOTIS PANTELIDIS, ANNA VASKU, ATHOL U. WELLS, KENNETH I. WELSH, and ROLAND M. DU BOIS

Interstitial Lung Disease Unit, Department of Occupational and Environmental Medicine, National Heart and Lung Institute, Imperial College of Science, Technology, and Medicine, London, England; Department of Immunology, Medical Faculty of Palacky University, and Department of Respiratory Medicine, University Hospital, Olomouc; and Institute of Pathological Physiology, Medical Faculty, Masaryk University, Brno, Czech Republic

Previous studies of the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in sarcoidosis have revealed both ethnic heterogeneity of I/D frequencies and controversy surrounding the association between the polymorphism and severity of disease. The objective of this study was, therefore, to clarify the role of the ACE I/D polymorphism in (1) disease susceptibility, (2) pulmonary disease severity (with particular reference to pulmonary fibrosis), and (3) pulmonary disease progression, in two distinct European sarcoidosis populations. Standard chest radiographic staging was performed on 118 UK and 56 Czech white patients with sarcoidosis at 2 yr from presentation. Pulmonary function data were analyzed, and patients were then categorized according to disease severity. A PCR-SSP assay was used to determine the ACE I/D genotype of each patient studied. The I/D allele frequencies from these patients were compared with frequencies from ethnically matched UK (n = 386) and Czech (n = 179) control subjects using a chi-square contingency table. No significant differences were seen in the distribution of the ACE I/D genotypes, allele frequencies or phenotype frequencies. Furthermore, no association was found between the ACE I/D polymorphism and pulmonary disease severity, fibrosis, and progression. We conclude that the ACE I/D polymorphism has no role in sarcoidosis susceptibility in European whites and that it is not a regulatory variant in this disease.

Keywords: ACE; polymorphism; susceptibility gene; sarcoidosis; ethnicity




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