Immunogenetics of HLA class II in Israeli Ashkenazi Jewish, Israeli non-Ashkenazi Jewish, and in Israeli Arab IDDM patients

The distribution of HLA class II alleles and genotypes in IDDM patients was examined in the three main Israeli ethnic groups: Ashkenazi Jews, non-Ashk enazi Jews, and Arabs. Molecular sequence specific oligonucleotide probe an alysis was performed for DRB1, DQA1, and DQB1 genes. The DRB1*03011, DQA1*0 5 DQB1*02/DRB1*0402, DQA1*03, DQB1*0302 genotype was found to be the main s usceptibility genotype in all three groups, with differences in the degree of association. In addition to DRB1*0402 (more frequent among Ashkenazi Jew s), DRB1*0405, another subtype of DRB1*04, was found ro be more prevalent, among non-Ashkenazi Jews and Arabs. Many alleles were found to be negativel y associated with insulin dependent diabetes mellitus (IDDM). This could br a result of the high frequency of susceptible alleles, Dr of linkage diseq uilibrium to a primary negatively associated allele. The strongest negative association was observed for DQB1*0301 in all three ethnic groups. The all eles DRB1*1401, DRB1*1501, DQB1*05031, DQB1*0602, and DQB1*0609 were not de tected in any of the 202 IDDM patients, and are probably either strongly pr otective or in linkage with such alleles. Despite the differences found bet ween the three ethnic groups, an overall analysis shows that the DRB1*04 al leles that account for susceptibility to IDDM in the Israeli population (DR B1*0402 and *0405) are the same as those responsible for susceptibility to IDDM in a number of other Mediterranean populations. In contrast, the susce ptible allele in most Caucasian populations is DRB1*0401. It is noteworthy that the susceptible alleles DRB1*0402/05 for Mediterranean and DRB1*0401 f or Caucasian populations are also frequent in the respective healthy popula tions. These findings support the results obtained in other studies, which point to a genetic relationship between the Israeli and Mediterranean popul ations. Human Immunology, 62, 85-91 (2001). (C) American Society for Histoc ompatibility and Immunogenetics, 2001. Published by Elsevier Science Inc.