The genotypes of HLA-A,-B, and -C, were determined by PCR-SSOP using the WAKFlow HLA typing kit (Wakunaga, Hiroshima, Japan) (19) and the Luminex Multi-Analyte Profiling system (xMAP, Luminex Corporation, Austin, TX,

USA) (18, 19), according to the manufacturer’s instructions. For most of the analyses, we used only 2-digit types. Comparisons of level of pVL and CD4+ T cell decline between the two groups were performed by the Mann–Whitney U test, and a q-value approach was adopted for multiple comparisons (20). q < 0.2 were considered statistically significant. In the present study, we aimed to identify Selleck Obeticholic Acid HLA class I alleles that are associated with slow or rapid HIV disease progression in the Japanese population, and to investigate changes in the impact of individual HLA class I allele expression on disease progression at the population level over time. To this end, we initially sought to characterize HLA class I allele distribution in the Japanese population as compared to that in Western countries. We expected the Japanese to have a narrower spectrum of HLA class I types, since Japan is geographically isolated and had closed the door to other nations for a long time, as a result having very few immigrants. We reviewed the literature and compared HLA distributions in the general population

between Japan and the USA (Fig. 1). We found that the total number of HLA class I alleles with over 1% of allelic frequency in the Japanese population was only 29 (A: 6, B: 15 and Cw: 8, n= 1018, Fig. 1a), which is considerably smaller than that found in European-Americans (total: Selleckchem Caspase inhibitor 46, A: 14, B: 19, Cw: 13, n= 265, Fig. 1b), and in African-Americans (total: 50, A: 16, B: 21, Cw: 13, n= 252, Fig. 1c) (18, 21), confirming most that the Japanese population is genetically much less diverse as compared to these other major ethnic groups. Furthermore, we noticed unique features in

the Japanese population: (1) over 70% of people express HLA-A24; (2) the major protective alleles against HIV disease progression found in North America and in African countries are rarely seen (B27: 0.05% and B57: 0.0% of allelic- frequency) (18); (3) the major detrimental alleles (B*5802, B*3502/3503 and B53) are not observed at all (18); and (4) HLA-B51, which is widely known to be protective in Caucasians, is common in the Japanese population, almost 20% of people expressing this allele (Fig. 1a). These results indicate that HIV-1 circulating in this unique Asian population has been exposed to a distinct environment in terms of CTL selection pressures as compared to HIV-1 circulating in Caucasian or African populations. Given the distinctive HLA distribution in the Japanese population, we sought to find class I alleles associated with slow or rapid disease progression that have never been reported from the Western countries.