Am. J. Respir. Crit. Care Med., Volume 162, Number 3, September 2000, 1000-1003

CC Chemokine Receptor Gene Polymorphisms in Czech Patients with Pulmonary Sarcoidosis

MARTIN PETEK, JIÍ DRÁBEK, VÍTZSLAV KOLEK, JAROSLAV ZLÁMAL, KENNETH I. WELSH, MICHAEL BUNCE, EVEN WEIGL, and ROLAND DU BOIS

Departments of Immunology and Respiratory Medicine, PalackýUniversity, Olomouc, Czech Republic; Churchill Hospital Oxford, United Kingdom; and Interstitial Lung Disease Unit, Royal Brompton Hospital, London, United Kingdom

Genes for the chemokine receptors CCR5 and CCR2 are characterized by polymorphisms resulting in a nonfunctional receptor expression. Ligands for CCR2 and CCR5 (chemokines monocyte chemotactic protein-1 [MCP-1] and RANTES) are implicated in the pathogenesis of sarcoidosis. We have, therefore, analyzed polymorphisms of CCR5 (32-bp deletion in CCR5 gene [32]) and of CCR2 (replacement of valine by isoleucine in CCR2 gene [64I]) in 66 Czech patients with sarcoidosis in comparison with a representative sample of Czech normal population. The frequencies of CCR532 and CCR2-64I polymorphisms in patients with sarcoidosis were different from that in control subjects. CCR532 allelic frequency was significantly increased in patients. By contrast, the CCR2-64I allele was more frequent in control subjects; however, the difference did not attain significance. Interestingly, the CCR532 allele was associated with clinically more apparent disease: it was present in 39.1% of patients requiring corticosteroids but only in 16.7% patients who did not need therapeutic intervention (odds ratio [OR] = 2.9). When patients requiring corticosteroids were compared with control subjects, the differences in the CCR532 frequencies were enhanced (p < 0.01). In conclusion, the observed association of CCR532 and CCR2-64I with sarcoidosis implicates a role for these polymorphisms in disease susceptibility and protection.

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