The role of the C-C chemokine receptor 2 gene polymorphism V641 (CCR2-641) in sarcoidosis in a Japanese population

A number of chemokines are produced by alveolar cells in the course of inflammatory reactions of sarcoidosis. C-C chemokine receptor 2 (CCR2) is a prominent receptor for the monocyte chemoattractant protein (MCP) group of C-C chemokines. A transition causing a valine to isoleucine substitution in transmembrane domain I of the CCR2 gene (CCR2-641) that has a protective effect against the progression of human immunodeficiency virus-1 (HIV-1) disease has been described. To elucidate the role of this CCR2 polymorphism in sarcoidosis, we investigated the distribution of the CCR2-641 in 100 subjects with sarcoidosis (40.2 +/- 18.6 yr [mean +/- SD], 37:63 [male:female]) and 122 healthy control subjects (44.4 +/- 14.1 yr, 75:47). The distribution of the CCR2-641 allele was significantly different between subjects with sarcoidosis and healthy control subjects (p < 0.001). The presence of the CCR2-641 allele conferred a lower risk for the development of sarcoidosis (adjusted odds ratio = 0.369, 95% CI = 0.203 to 0.673). Our study suggests that this polymorphism may play a role in the pathogenesis of sarcoidosis, and further studies are needed to define the role of CCR2-641.