HLA-A and DPB1 loci confer susceptibility to Graves' disease.
To investigate HLA-linked genetic factors involved in the pathogenesis of Graves' disease, 76 patients and 317 healthy controls in the Japanese population were examined for HLA-A, B, C, DR, and DQ specificities by serologic typing and for HLA-DPB1 alleles by DNA typing by using the PCR-SSOP method. The frequencies of HLA-A2, B46, Cw11, and DPB1*0501 were increased and those of HLA-A24, B7, Bw52, and DR1 were decreased in the patients. The increased frequencies of HLA-A2 and DPB1*0501 in the patients were statistically significant when the corrected p value (pc) was applied (pc < 0.02 and pc < 0.002, respectively). ORs for a risk to develop the disease were calculated among individuals positive for DPB1*0501 and/or HLA-A2, and the highest OR (10.5) was observed in individuals possessed both DPB1*0501 and HLA-A2. This observation suggests a synergic involvement of a HLA class II allele (DPB1*0501) and an HLA class I allele (HLA-A2) in the pathogenesis of Graves' disease.
Dong
R P
RP
Department of Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Kimura
A
A
Okubo
R
R
Shinagawa
H
H
Tamai
H
H
Nishimura
Y
Y
Sasazuki
T
T
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D002648:Child; D004198:Disease Susceptibility; D005260:Female; D005787:Gene Frequency; D005805:Genes, MHC Class I / Q000502:physiology; D005802:Genes, MHC Class II / Q000502:physiology; D008040:Genetic Linkage; D006111:Graves Disease / Q000235:genetics*; D006680:HLA Antigens / Q000235:genetics; D015234:HLA-A Antigens / Q000235:genetics*; D006682:HLA-DP Antigens / Q000235:genetics*; D059868:HLA-DP beta-Chains; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D017386:Sequence Homology, Amino Acid
D006680:HLA Antigens; D015234:HLA-A Antigens; D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen