CC chemokine receptor gene polymorphisms in Czech patients with pulmonary sarcoidosis.
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.
Petrek
M
M
Departments of Immunology and Respiratory Medicine, PalackýUniversity, Olomouc, Czech Republic. petrekm@fnol.cz
Drábek
J
J
Kolek
V
V
Zlámal
J
J
Welsh
K I
KI
Bunce
M
M
Weigl
E
E
Du Bois
R
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D018153:Czech Republic; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000235:genetics*; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000235:genetics*; D012507:Sarcoidosis / Q000235:genetics*
C515334:CCR2 protein, human; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine