Genotypes and Haplotypes of CCR2 and CCR3 Genes in Japanese Cedar Pollinosis

Abstract

Whole genome scan analyses have revealed that the chromosomal region 3p21.3, which contains a gene cluster of the CC chemokine receptor, is possibly critical for the pathogenesis of allergic inflammation. Japanese cedar pollinosis is mediated by a type I allergy and induces seasonal rhinitis and conjunctivitis in humans as the most common form of hay fever in spring in Japan, although the candidate genes for cedar pollinosis remain to be elucidated. We sequenced CCR1, CCR2, CCR3, CCR5, and CCXCR1 using the PCR restriction fragment length polymorphism method in subjects with cedar pollinosis and controls. We found 8 polymorphisms of A111G, Arg127Cys and Arg252Gln in CCXCR1, T885C in CCR1, Val64Ile and T780C in CCR2, T51C in CCR3 and Arg223Gln in CCR5. The transmission disequilibrium test using 60 children with pollinosis and their parents and an association study using unrelated adult subjects (151 patients and 157 controls) showed a significant association of 64Ile in CCR2 and 51C in CCR3 with cedar pollinosis. The frequency of haplotype 64Ile/780C/51C in pollinosis was significantly higher than in controls. Our results suggest that CCR2 and CCR3 genes are candidate genes for Japanese cedar pollinosis.