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

HLA is an important etiologic genetic factor in Type I diabetes and specifi c 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 DQ B1 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 sus ceptible alleles or haplotype to Type I diabetes while DR-DO haplotype stud ies suggested the important role of DR and DQ alleles in susceptibility and resistance in Japanese patients. Based on the analysis of 90 Japanese pati ents with childhood onset Type I diabetes and 136 unrelated healthy Japanes e controls by polymerase chain reaction-restriction fragment polymorphism m ethod (PCR-RFLP), we report here the association of Type I diabetes with DP B1*0201 (relative risk = 2.29; P-c = 0.027) in this population. Comparison of linkage disequilibrium patterns between patients and controls showed tha t the significantly high prevalence of DPB1*0201 among patients cannot be a ttributed simply to linkage disequilibrium with susceptible DRB1 alleles an d DQA1-DQB1 haplotypes, Our results suggest that in addition to alleles at the DRB1, DQA1, DQB1 loci, polymorphism at DPB1 locus also influences the r isk of Type I diabetes. (C) 2000 Elsevier Science Ireland Ltd. All rights r eserved.