HLA-DRB1*04 and susceptibility to type 1 diabetes mellitus in a German/Belgian family and German case-control study

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Abstract
HLA‐DR4 is a primary disease association marker in type 1 diabetes mellitus (IDDM). We therefore analyzed the transmission of 228 DR4+ haplotypes in 183 families with an IDDM proband (95 from Germany and 88 from Belgium). In a separate case‐control data set, we investigated the HLA‐DRB1*04 and DQ allele distribution in 245 IDDM patients and 177 controls from Germany, all DR4 positive. HLA‐DRB1*0401 and *0402 linked to DQB1*0302 were significantly more often transmitted to patients in the studied families (81% and 89%) in contrast to DRB1*0401‐DQB1*0301 (33%). The case‐control study of HLA‐DQB1*0302+ individuals revealed ‐DRB1*0405 to be more frequent in patients with IDDM and HLA‐DRB1*0403 and ‐DRB1*0404 to be less frequent. HLA‐DQA1*0102‐DQB1*0602 and ‐DQA1*0501‐DQB1*0301 in trans complementation with DRB1*0401‐DQB1*0302 were also significantly less frequent in IDDM patients (P−7 and PHLA‐DRB1*0403 and ‐DQB1*0301 alleles in cis as well as protective DQ haplotypes in trans, confer dominant protection against IDDM in a German / Belgian population.