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      HLA DPB1*0201 gene confers disease susceptibility in japanese with childhood onset type I diabetes, independent of HLA-DR and DQ genotypes.

      Diabetes Research and Clinical Practice

      Polymorphism, Restriction Fragment Length, Child, Child, Preschool, Diabetes Mellitus, Type 1, genetics, immunology, Female, Genetic Predisposition to Disease, Genotype, HLA-DP Antigens, Adolescent, HLA-DP beta-Chains, HLA-DQ Antigens, HLA-DR Antigens, Humans, Infant, Newborn, Japan, Linkage Disequilibrium, Male

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          HLA is an important etiologic genetic factor in Type I diabetes and specific HLA-class II genes are closely related to the onset of the disease. Many differences in the patterns of susceptible and resistant DRB1, DQA1, and DQB1 genes have been observed among various ethnic groups. We have previously shown that DRB1*0405, DRB1*0901 and DQA1*0301-DQB1*0302 were the major susceptible alleles or haplotype to Type I diabetes while DR-DQ haplotype studies suggested the important role of DR and DQ alleles in susceptibility and resistance in Japanese patients. Based on the analysis of 90 Japanese patients with childhood onset Type I diabetes and 136 unrelated healthy Japanese controls by polymerase chain reaction-restriction fragment polymorphism method (PCR-RFLP), we report here the association of Type I diabetes with DPB1*0201 (relative risk = 2.29; Pc = 0.027) in this population. Comparison of linkage disequilibrium patterns between patients and controls showed that the significantly high prevalence of DPB1*0201 among patients cannot be attributed simply to linkage disequilibrium with susceptible DRB1 alleles and DQA1-DQB1 haplotypes. Our results suggest that in addition to alleles at the DRB1, DQA1, DQB1 loci, polymorphism at DPB1 locus also influences the risk of Type I diabetes.

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