Celiac disease is associated with an extended HLA-DR3 haplotype which includes HLA-DPw1.
HLA-DP polymorphism was examined among celiac disease patients and controls. Restriction fragment length polymorphism (RFLP) genotyping showed a significant association of DPw1 in celiac disease (32/80) compared with controls (6/53, p = 0.0002). DPw1 typing by RFLP was verified using DPB1-amplified DNA and an oligonucleotide probe specific for the DPw1-associated DPB1 gene. The RFLP-assigned DPw1 genotype corresponded closely to the binding pattern of the sequence-specific oligonucleotide probe, although discrepancies did occur. The association between celiac disease and DPw1, however, remained. Oligonucleotide probe specificity was confirmed by sequencing DPB1-amplified DNA from four DPw1-genotyped celiacs. DPw1 is only present in celiacs who genotype DR3a-positive. Of DR3a controls 24% are DPw1-positive compared with 5% of non-DR3a controls (p = 0.03), suggesting that an extended DR3a, DPw1 haplotype occurs in the control population. This haplotype forms a large proportion of the DR3a haplotypes predisposing to celiac disease. Alternatively, DPw1 may represent an independent risk factor inherited in linkage with HLA-DR3 and -DQw2. Although predisposition to celiac disease is likely to be mediated by a specific DQ alpha/DQ beta heterodimer, a direct role for the DPw1 antigen cannot be discounted.
Hall
M A
MA
Molecular Immunogenetics Laboratory, U.M.D.S., Guy's Hospital, London, U.K.
Lanchbury
J S
JS
Bolsover
W J
WJ
Welsh
K I
KI
Ciclitira
P J
PJ
D001483:Base Sequence; D015139:Blotting, Southern; D002446:Celiac Disease / Q000235:genetics / Q000276:immunology*; D016009:Chi-Square Distribution; D003001:Cloning, Molecular; D005838:Genotype; D006682:HLA-DP Antigens / Q000235:genetics* / Q000276:immunology; D059868:HLA-DP beta-Chains; D015803:HLA-DR3 Antigen / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes / Q000235:genetics*; D006650:Histocompatibility Testing; D006801:Humans; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics / Q000276:immunology; D012150:Polymorphism, Restriction Fragment Length
D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C054111:HLA-DPw1 antigen; D015803:HLA-DR3 Antigen; D015345:Oligonucleotide Probes