Genes for the chemokine receptors CCR5 and CCR2 are characterized by polymo
rphisms 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, analyze
d polymorphisms of CCR5 (32-bp deletion in CCR5 gene [Delta 32]) and of CCR
2 (replacement of valine by isoleucine in CCR2 gene [641]) in 66 Czech pati
ents with sarcoidosis in comparison with a representative sample of Czech n
ormal population. The frequencies of CCR5 Delta 32 and CCR2-641 polymorphis
ms in patients with sarcoidosis were different from that in control subject
s. CCR5 Delta 32 allelic frequency was significantly increased in patients.
By contrast, the CCR2-641 allele was more frequent in control subjects; ho
wever, the difference did not attain significance. Interestingly, the CCR5
Delta 32 allele was associated with clinically more apparent disease: it wa
s 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 subject
s, the differences in the CCR5 Delta 32 frequencies were enhanced (p < 0.01
). In conclusion, the observed association of CCR5 Delta 32 and CCR2-641 wi
th sarcoidosis implicates a role for these polymorphisms in disease suscept
ibility and protection.