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 DRB1*1501, DQB1*0602 in Caucasoids and with DQB1*0602 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 (DPB1*0301) 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 DQB1*0602. PCR-RFLPs were used to determine distributions of 20 HLA-DPB1 alleles in 41 Australian MS patients and 67 controls of known DQB1*0602 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 DQB1*0602 did not differ, but in those MS patients lacking DQB1*0602, the DPB1*0301 antigen (phenotype) frequency was significantly (p = 0.006) increased (50.0%) when compared with DQB1*0602-negative controls (9.1%). DPB1*0301 was associated (p = 0.003) with DQB1*0402 (DR8) in Caucasoid MS patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Dekker
J W
JW
Human Genetics Group, John Curtin School of Medical Research, Australian National University, Canberra.
Easteal
S
S
Jakobsen
I B
IB
Gao
X
X
Stewart
G J
GJ
Buhler
M M
MM
Hawkins
B R
BR
Higgins
D A
DA
Yu
Y L
YL
Serjeantson
S W
SW
D000483:Alleles; D044466:Asian People / Q000235:genetics*; D001315:Australia; D001327:Autoimmune Diseases / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D006682:HLA-DP Antigens / Q000235:genetics*; D059868:HLA-DP beta-Chains; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006239:Haplotypes; D006723:Hong Kong; D006801:Humans; D015810:Linkage Disequilibrium; D009103:Multiple Sclerosis / Q000235:genetics*; D012307:Risk Factors; D044465:White People / Q000235:genetics*
D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen