title: HLA-DRB1*0403 is associated with dominant protection against IDDM in the general Dutch population and subjects with high-risk DQA1*0301-DQB1*0302/DQA1*0501-DQB1*0201 genotype.
abstract: Insulin-dependent (Type 1) diabetes mellitus (IDDM) is a genetically controlled T-cell mediated autoimmune disease. Recently, subtyping of HLA-DRB1*04 identified the HLA-DRB1*0403 allele to be associated with protection in Caucasoids with the highest risk heterozygous genotype DQA1*0301-DQB1*0302/DQA1*0501-DQB1*0201. Some studies confirmed this finding, but other reports were not consistent with a dominantly protective trait. We here report the frequency of HLA-DRB1*0403 in a large cohort (n=200) of Dutch patients with IDDM, their first-degree family members (n=370), and random controls (n=420) of the general population in The Netherlands. We found that HLA-DRB1*0403 is strongly associated with dominant protection against development of IDDM in unrelated subject, even in the context of the highest risk HLA-DQ phenotypes and HLA-DR4-DQB1*0302 (P < 0.0001).
authors.affiliation: Department of Immunohaematology & Blood Bank, Leiden University Medical Centre, The Netherlands. broep@pobox.leidenuniv.nl
authors.forename: B O
authors.initials: BO
authors.lastname: Roep
authors.forename: R
authors.initials: R
authors.lastname: Schipper
authors.forename: W
authors.initials: W
authors.lastname: Verduyn
authors.forename: G J
authors.initials: GJ
authors.lastname: Bruining
authors.forename: G M
authors.initials: GM
authors.lastname: Schreuder
authors.forename: R R
authors.initials: RR
authors.lastname: de Vries
mesh_terms: D000483:Alleles; D003718:Denmark / Q000453:epidemiology; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D012307:Risk Factors
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