Characterization of CCR5 chemokine receptor gene polymorphisms in Japanese and Thai populations (45.11)

Abstract

Abstract Variations in the human CCR5 gene may alter the expression and/or function of the protein product, thereby altering chemokine binding/signaling or HIV infection of the cells that normally express CCR5 protein. We performed a systematic survey of genetic variations in the entire CCR5 gene as well as CCR2V64I in 50 Japanese subjects and evaluated the effects of those variations on CCR5 promoter activity. We also analyzed CCR5 promoter and CCR2V64I genotypes in 80 more Japanese and 186 Thais. Two types of non-synonymous substitutions in Japanese CCR5 gene were found. Our results showed several novel characteristics of the CCR2-CCR5 haplotype structure that were not reported from studies on Caucasians and African-Americans. Specifically, we were able to show that the G allele at position -2852 from the CCR5 translational start codon in Japanese and Thais is the representative of the CCR5 promoter haplotype that was reported to be associated with rapid progression to AIDS in HIV-infected individuals. Furthermore, nearly all non-synonymous polymorphisms in Japanese CCR5 gene occurred in haplotypes with elevated promoter activity. We thus hypothesized that there was certain selective pressure favoring low levels of CCR5 expression during human evolution.