Complete association of the HLA-DRB1*04 and -DQB1*04 alleles with Vogt-Koyanagi-Harada's disease.
VKH disease is a bilateral panuveitis and has been known to be closely associated with the particular HLA class II antigens HLA-DR4 and -DQ4, defined by serologic typing. In this study, 63 Japanese VKH patients were analyzed for HLA class II alleles at the DNA level using the PCR-RFLP method. The DRB1*04 alleles encoding the serologic specificity DR4 were found in 100% of the VKH patients carrying DRB1*0405 or DRB1*0410. By statistical analysis, only DRB1*0405 was found to be significantly increased as compared to the healthy controls (RR = 46.7 and pc < 1 x 10(-5)). As to the DQB1 locus, all the patients carried DQB1*0401 or DQB1*0402 expressing the serologic DQ4 specificity, which is in a strong linkage disequilibrium with DRB1*0405 or DRB1*0410 in a Japanese population, respectively. Only DQB1*0401 showed a statistically significant increase as compared to the healthy controls (RR = 41.3 and pc < 1 x 10(-5)). Comparison of the amino acid sequences of these DRB1 and DQB1 alleles indicates that Ser at position 57 of DRB1 and/or Glu at position 70 and Asp at position 71 of DQB1 plays a crucial role in determining the susceptibility to VKH disease.
Shindo
Y
Y
Department of Ophthalmology, Yokohama City University School of Medicine, Japan.
Ohno
S
S
Yamamoto
T
T
Nakamura
S
S
Inoko
H
H
D000328:Adult; D000368:Aged; D000483:Alleles; D000595:Amino Acid Sequence; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006683:HLA-DQ Antigens / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D014607:Uveomeningoencephalitic Syndrome / Q000235:genetics* / Q000276:immunology*
D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II