The objective of the present study was to clarify the pathological roles of CCR1 and IL10 loci identified by previous BD genome-wide association studies (GWASs).
Along with human leukocyte antigen gene encoding B*51 (HLA-B*51) and areas including the major histocompatibility complex class I, genome-wide association studies have recognized numerous other BD susceptibility genes including those encoding interleukin (IL)-10, IL-12 receptor β 2 (IL-12RB2), IL-23 receptor (IL-23R), C-C chemokine receptor 1 gene, signal transducer and activator of transcription 4 (STAT4), endoplasmic reticulum aminopeptidase (ERAP1), and genes encoding killer cell lectin-like receptor family members (KLRC4-KLRK1).
Moreover, we need to determine allele-specific effects of ERAP1 variants in the context of HLA-B*51 and HLA-Cw*6, which are associated with Behçet's disease and psoriasis, respectively.
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.
Therefore, we performed HLA-B*51 allele genotyping by the polymerase chain reaction-sequencing based typing (PCR-SBT) method in order to investigate whether there is any correlation of one particular B51-associated allele with Japanese BD.
Our findings suggest that gene-gene interactions between HLA-B*51 and ERAP1 variants is important for BD development, however, ERAP1 variants which interact with HLA-B*51 may differ among disease phenotypes or populations.
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.
In this Perspectives article, we describe how Behçet disease and several clinically distinct spondyloarthropathies-all associated with MHC class I (MHC-I) alleles such as HLA-B(*)51, HLA-C(*)0602 and HLA-B(*)27 and epistatic ERAP-1 interactions-have a shared immunopathogenetic basis.
HLA-C1<sup>Asn80</sup> showed a protective effect against BD, whereas HLA-C2<sup>Lys80</sup>, HLA-B-Bw4<sup>Ile80</sup>, HLA-B5, and HLA-B51 were associated with a susceptibility risk for BD.
This study was conducted on the two most consistently BS-associated ERAP1 polymorphisms, rs17482078 (NG_027839.1:g.35983G>A) and rs27044 (NG_027839.1:g.35997C>G) to analyse their distribution in 55 Italian BS patients and 65 ethnically matched controls (healthy controls, HC) and to test their association with BS risk.
Behçet's disease (BD), a multi-organ inflammatory disorder, is associated with the presence of the human leukocyte antigen (HLA) HLA-B*51 allele in many ethnic groups.
Moreover, we need to determine allele-specific effects of ERAP1 variants in the context of HLA-B*51 and HLA-Cw*6, which are associated with Behçet's disease and psoriasis, respectively.
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.
Here, eight polymorphic microsatellite markers, distributed over a 900-kb region surrounding the HLA-B locus, were subjected to association analysis for Behçet disease.