HLA-DPB1 alleles correlate with risk for multiple sclerosis in Caucasoid and Cantonese patients lacking the high-risk DQB1*0602 allele.

Multiple sclerosis (MS) is a demyelinating disease associated with the HLA-DR2-related haplotype DRB11501, DQB10602 in Caucasoids and with DQB10602 in DR2-positive Cantonese. However, many MS patients do not have the high-risk HLA-D determinants and alternative genes may contribute to the pathogenesis of MS. One candidate gene is HLA-DPB1. Our reanalysis of five earlier reports of HLA-DPB1 antigen distributions in Caucasoid MS patients shows a consistent and highly significant increase (p = 1.5 x 10(-5)) in frequency of HLA-DPw3 in the combined data set. This study tests whether HLA-DPw3 (DPB10301) is also increased in frequency in Australian and Cantonese MS patients and whether any distortion in DPB1 allelic distributions can be attributed to linkage disequilibrium with DQB10602. PCR-RFLPs were used to determine distributions of 20 HLA-DPB1 alleles in 41 Australian MS patients and 67 controls of known DQB10602 status and in 11 Cantonese MS patients and 33 controls positive for HLA-DR2. HLA-DP distributions in Australian MS patients and controls positive for DQB10602 did not differ, but in those MS patients lacking DQB10602, the DPB10301 antigen (phenotype) frequency was significantly (p = 0.006) increased (50.0%) when compared with DQB10602-negative controls (9.1%). DPB10301 was associated (p = 0.003) with DQB10402 (DR8) in Caucasoid MS patients.(ABSTRACT TRUNCATED AT 250 WORDS)