These results indicated that a non-HLA gene located around the TNF gene region centromic of the HLA-B gene was a candidate to control the genetic susceptibility to Behçet's disease.
These results indicated that the primary and primordial gene(s) responsible for the susceptibility to BD, especially related to ocular lesions, were not located in the HLA class II gene region but were in or very close to the HLA-B locus in the class I region.
Specific HLA antigens were also found in other forms of uveitis such as Reiter's disease (HLA-B 27), Behcet's syndrome (HLA-B 5), VKH syndrome (HLA-Bw 22J) and ocular histoplasmosis (HLA-B 7).
One of the HLA-B molecules investigated here, HLA-B*5101, is associated with Behçet's disease, a multisystemic inflammatory disease affecting various organs.
These facts suggest that the pathogenic gene of Behçet's disease is not the HLA-C gene (HLA-Cw*14 and/or HLA-Cw*15) but the HLA-B gene (HLA-B51) itself or a non-HLA gene residing in the centromeric side of the HLA-B gene rather than in the telomeric side around the HLA-C gene.
HLA-B51 molecules themselves may be responsible, at least in part, for the neutrophil hyperfunction in Behçet's disease; a significant correlation was observed between the neutrophil hyperfunction and the possession of HLA-B51 phenotype, regardless of the presence of the disease, in both humans and HLA-B transgenic mice.
In order to investigate the influence of the MICB gene, located about 120 kb centromeric of the HLA-B gene, on the susceptibility to BD, (CA/TG) dinucleotide repeat microsatellite polymorphism in intron 1 of the MICB gene was investigated among 77 Japanese patients with BD, 60 randomly selected controls and 28 HLA-B51-positive unrelated healthy controls.
The fact that different HLA-B51 subtypes are associated with BD could suggest that common motifs shared by HLA-B51-related alleles are involved in the susceptibility to BD or, in the light of recent studies, that a mutation causing the susceptibility to BD occurred in the B*5101 haplotype, close to HLA-B gene, before the divergence of B*5108 from the B*5101 allele.
Here, eight polymorphic microsatellite markers, distributed over a 900-kb region surrounding the HLA-B locus, were subjected to association analysis for Behçet disease.
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.