HLA class II immunogenetics of IDDM in Yemenite Jews

The association between HLA-DR and DQ and insulin dependent diabetes mellitus (IDDM) was analyzed in 47 patients and 76 controls of Yemenite Jewish origin. The IDDM susceptibility alleles DRB1*03011, DQA1*0501, DQB1*02 and DRB1*0402, DQA1*0301, DQB1*0302 found in Caucasians had a very strong predisposing effect also in the Yemenite IDDM group. The DRB1*07, DQA1*0201 and DQB1*02 alleles were found to have a strong negative association with IDDM. None of the patients carried DRB1*07 and DQA1*0201 compared with healthy controls (43.7%). Our analysis revealed that the DRB1*03011 DQA1*0501 DQB1*02/DRB1*04 DQA1*03 DQB1*0302 heterozygous genotype confers the highest susceptibility (59.6% in patients vs. 0% in controls). The homozygous DRB1*03 and DRB1*04 genotypes were also found to be positively associated with the disease. 81% of the patients compared to 1.3% of controls carried the susceptibility alleles on both haplotypes. In conclusion, the development of IDDM in Yemenite Jews is strongly dependent on the presence of the susceptibility HLA alleles and on the absence of the DRB1*07 haplotype. The Yemenite Jewish group is uniquely homogenous with regard to genetic susceptibility factors involved in the process of IDDM, and may thus be an ideal model for further genetic studies.