Genetics of Behçet disease inside and outside the MHC.
BACKGROUND
Behçet disease (BD) is a rare, chronic, systemic, inflammatory disorder characterised by recurrent ocular, genital and skin lesions. Although its aetiology is still uncertain, an intricate interplay between the environment (eg, viruses) and the host seems to initiate and/or perpetuate the disease, although the mechanism remains speculative. Since the identification of HLA-B*5101 (and more recently of MICA) as a susceptibility locus for BD, the identification of additional genetic locus/loci, whether inside, or perhaps more importantly outside the MHC has clearly stalled.


OBJECTIVE
To carry out a genome-wide association study (GWAS) of BD.


METHODS
300 Japanese patients with BD and an equal number of controls were recruited. The samples were screened using a dense panel of 23 465 microsatellites (MS) covering the entire genome.


RESULTS
The six best (of a total of 147) positively associated MS with BD were identified. Of these six, two were located within the human leucocyte antigen (HLA) class I region itself. Although one of these was clearly reminiscent of the association with HLA-B, the second, not in linkage disequilibrium with the former, was in the telomeric side of the class I region and remained to be formally identified. HLA genotyping and haplotype analysis conclusively led to the deciphering of a dual, independent, contribution of two HLA alleles to the pathogenesis of BD: HLA-B*5101 and HLA-A*26.


CONCLUSIONS
This GWAS highlights the premier genetic susceptibility locus for BD as the major histocompatibility complex itself, wherein reside two independent loci: HLA-B and HLA-A.
Meguro
Akira
A
Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Kanazawa-ku, Yokohama, Kanagawa, Japan.
Inoko
Hidetoshi
H
Ota
Masao
M
Katsuyama
Yoshihiko
Y
Oka
Akira
A
Okada
Eiichi
E
Yamakawa
Ryoji
R
Yuasa
Takenosuke
T
Fujioka
Toshihiko
T
Ohno
Shigeaki
S
Bahram
Seiamak
S
Mizuki
Nobuhisa
N
D001528:Behcet Syndrome / Q000235:genetics*; D016022:Case-Control Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D015234:HLA-A Antigens / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics*; D006239:Haplotypes; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D015810:Linkage Disequilibrium; D018895:Microsatellite Repeats; D010641:Phenotype
D015234:HLA-A Antigens; D015235:HLA-B Antigens