title: HLA-DPB1*0401 is associated with dominant protection against type 1 diabetes in the general Saudi population and in subjects with a high-risk DR/DQ haplotype.
abstract: The human leukocyte antigen (HLA) class II DQB1*0201/0202-DRB1*04 genotype has been identified as predisposing to type 1 diabetes [insulin-dependent diabetes mellitus (IDDM)] in the Saudi Arabian population (P = 0.0002; odds ratio = 0.67; 95% confidence interval = 0.009-0.381). In this study, we searched for a factor at the DPB1 locus by analysing DPB1 polymorphism using sequence-based typing in 86 Saudi IDDM patients and control subjects, all carrying the HLA-DRB1*04/DQB1*02 haplotype or the known susceptibility allele DQB1*0201/0202. Significant protection was conferred by DPB1*0401, which was observed in 17 of 50 control subjects (55%) and 2 of 36 IDDM patients (5%) with the DQB1*0201/0202 allele (P = 0.0012; odds ratio = 8.75; confidence interval = 1.72-59.70). Our data showing a high frequency of the DPB1*0401 allele even in the presence of the predisposing DQB1*02 allele in healthy subjects may indicate a protective effect of this combination of HLA alleles against type 1 diabetes. This finding supports the hypothesis that protective HLA class II genes can override the risk conferred by HLA-DQ susceptibility alleles. Further studies using larger cohorts of control subjects and patients should be undertaken to confirm this observation.
authors.affiliation: Biological and Medical Research Department, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. khussein@kfshrc.edu.sa
authors.forename: K A
authors.initials: KA
authors.lastname: Al-Hussein
authors.forename: N R
authors.initials: NR
authors.lastname: Rama
authors.forename: M
authors.initials: M
authors.lastname: Ahmad
authors.forename: E
authors.initials: E
authors.lastname: Rozemuller
authors.forename: M G
authors.initials: MG
authors.lastname: Tilanus
mesh_terms: D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005799:Genes, Dominant; D020022:Genetic Predisposition to Disease; D006682:HLA-DP Antigens / Q000235:genetics* / Q000378:metabolism; D059868:HLA-DP beta-Chains; D006683:HLA-DQ Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D012529:Saudi Arabia
chemical_list: D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens