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

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<3x 10(-7) and P<0.02). In conclusion, HLA-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.

• Authors: H Donner, C Seidl, B Van der Auwera, J Braun, T Siegmund, J Herwig, I Weets, K H Usadel, K Badenhoop
• Journal: Tissue antigens (Tissue Antigens) Vol. 55 Issue 3 Pg. 271-4 (Mar 2000) ISSN: 0001-2815 [Print] England
• PMID: 10777104 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• HLA-DQ Antigens
• HLA-DQ alpha-Chains
• HLA-DQ beta-Chains
• HLA-DQA1 antigen
• HLA-DQB1 antigen
• HLA-DR Antigens
• HLA-DRB1 Chains
• HLA-DRB1*04:01 antigen

Topics

• Adolescent
• Adult
• Belgium
• Case-Control Studies
• Child
• Child, Preschool
• Diabetes Mellitus, Type 1 (genetics, immunology)
• Disease Susceptibility
• Female
• Genetic Predisposition to Disease (genetics)
• Germany
• HLA-DQ Antigens
• HLA-DQ alpha-Chains
• HLA-DQ beta-Chains
• HLA-DR Antigens (genetics)
• HLA-DRB1 Chains
• Humans
• Infant
• Male