CC chemokine receptor gene polymorphisms in Czech patients with pulmonary sarcoidosis

• Published in: American journal of respiratory and critical care medicine Vol. 162; no. 3; pp. 1000 - 1003
• Main Authors: PETREK, Martin, DRABEK, Jiri, KOLEK, Vitèzslav, ZLAMAL, Jaroslav, WELSH, Kenneth I, BUNCE, Michael, WEIGL, Evzen, BOIS, Roland M
• Format: Journal Article
• Language: English
• Published: New York, NY American Lung Association 01.09.2000
• Subjects: Adolescent; Adult; Aged; Biological and medical sciences; Czech Republic; Female; Genetic Predisposition to Disease - genetics; Humans; Male; Medical sciences; Middle Aged; Polymorphism, Genetic - genetics; Prognosis; Receptors, CCR2; Receptors, CCR5 - genetics; Receptors, Chemokine; Receptors, Cytokine - genetics; Sarcoidosis - genetics; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Czech Republic; Chemokine; Human; Corticosteroid; Lung disease; Gene; Sarcoidosis; Respiratory disease; Pathogenesis; Systemic disease; Polymorphism; Biological receptor
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/ajrccm.162.3.2001022

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 [Delta32]) 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 CCR5Delta32 and CCR2-64I polymorphisms in patients with sarcoidosis were different from that in control subjects. CCR5Delta32 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 CCR5Delta32 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 CCR5Delta32 frequencies were enhanced (p < 0.01). In conclusion, the observed association of CCR5Delta32 and CCR2-64I with sarcoidosis implicates a role for these polymorphisms in disease susceptibility and protection.