Association analysis between the MIC-A and HLA-B alleles in Japanese patients with Behçet's disease.
OBJECTIVE
Behçet's disease is known to be strongly associated with HLA-B51 in many different ethnic groups. Recently, by association analysis using refined microsatellite mapping, the critical region for Behçet's disease was identified as a 46-kb segment centromeric to the HLA-B gene. No expressed gene has been detected in this segment to date except the MIC-A (major histocompatibility complex class I chain-related gene A) and HLA-B genes. The present study was undertaken to analyze allelic distribution of the MIC-A gene among Japanese patients with Behçet's disease.


METHODS
Ninety-five Japanese patients with Behçet's disease and 116 ethnically matched healthy controls were enrolled in this study. MIC-A genotyping was performed by direct sequencing of polymerase chain reaction products from exons 2, 3, and 4 of the MIC-A gene, using an automated DNA sequencer.


RESULTS
The MIC-A009 allele was significantly more frequent in the patient group (69.5%) compared with the healthy controls (31.0%) (relative risk 5.06, corrected P = 0.00000024). In stratification analysis on the confounding effect of MIC-A009 on HLA-B*51 association and vice versa, Behçet's disease was distinctively associated only with HLA-B*51. Further, MIC-A009 was found to be strongly associated not only with HLA-B51, but also with HLA-B52, which was not increased in the patient group to any degree.


CONCLUSIONS
These results imply that the real disease susceptibility gene involved in the development of Behçet's disease is the HLA-B*51 allele itself and that the significant increase of the MIC-A009 allele in the patient group results secondarily from a strong linkage disequilibrium with HLA-B*51.
Mizuki
N
N
Yokohama City University School of Medicine, Yokohama, Japan.
Ota
M
M
Katsuyama
Y
Y
Yabuki
K
K
Ando
H
H
Goto
K
K
Nakamura
S
S
Bahram
S
S
Ohno
S
S
Inoko
H
H
D000328:Adult; D000483:Alleles; D001528:Behcet Syndrome / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D015234:HLA-A Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007564:Japan; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction
D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; D008565:Membrane Proteins