title: 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.affiliation: Medical Department I, Center of Internal Medicine, Johan Wolfgang Goethe-University Hospital, Frankfurt/Main, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Donner
authors.forename: C
authors.initials: C
authors.lastname: Seidl
authors.forename: B
authors.initials: B
authors.lastname: Van der Auwera
authors.forename: J
authors.initials: J
authors.lastname: Braun
authors.forename: T
authors.initials: T
authors.lastname: Siegmund
authors.forename: J
authors.initials: J
authors.lastname: Herwig
authors.forename: I
authors.initials: I
authors.lastname: Weets
authors.forename: K H
authors.initials: KH
authors.lastname: Usadel
authors.forename: K
authors.initials: K
authors.lastname: Badenhoop
mesh_terms: D000293:Adolescent; D000328:Adult; D001530:Belgium; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D004198:Disease Susceptibility; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005858:Germany; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D007223:Infant; D008297:Male
chemical_list: D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553505:HLA-DRB1*04:01 antigen