New variations of human CC-chemokine receptors CCR3 and CCR4.

CCR3 and CCR4 are the members of CC chemokine receptor family expressed on Th2 type CD4+ T cells. In this study, variation screening of the entire coding regions of CCR3 and CCR4 was performed, and possible association with several autoimmune diseases was tested, using the genomic DNA from 304 Japanese healthy individuals and 272 Japanese patients with rheumatic diseases. One non-synonymous substitution was identified in CCR3 gene, whereas in CCR4 gene, two non-synonymous and two synonymous substitutions were detected. Among the synonymous substitutions, CCR4 1014(C-->T) was observed in 7.2% of the healthy individuals and 6.6% of the patients, and was considered as a single nucleotide polymorphism. All other variations were observed in only one or two individuals. No significant association was observed between any of the variations and any of the rheumatic diseases. Among these variations, CCR3-C218S substitution coded by 652(T-->A) substitution was localized in the region conserved among the G protein coupled receptor family. Reactivity of eosinophils to the monoclonal antibody against CCR3 and the chemotaxis to eotaxin were slightly reduced in this patient as compared with healthy controls or a patient with Behçet disease homozygous for the common allele, while CCR3 mRNA level was not different. These findings suggest that CCR3-C218S substitution may lead to the reduced function of CCR3 at the protein level. Further study will be of interest to test whether CCR3-C218S variation or any of the CCR4 variations has a significant role in rendering susceptibility to immunological diseases or resistance to HIV infection.