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Behçet’s Disease (BD) pathogenesis remains unclear, but some genetic loci and environmental factors are proposed to play a role. Here, we investigate the association of the endoplasmic reticulum aminopeptidase-1 ( ERAP1 ) gene variants and  HLA-B*51  with BD susceptibility and clinical manifestations in Iranian patients. In the study, 748 BD patients and 776 healthy individuals were included. The MGB-TaqMan Allelic Discrimination method was used to genotype 10 common missense single nucleotide polymorphisms (SNPs) and one intronic SNP in the  ERAP1  gene region. We found no significant association between the 11 SNPs and BD in allelic and genotypic association tests. However, rs30187 showed the strongest association with BD in the recessive genotype model of the risk T allele in  HLA-B*51  carriers. Although this became insignificant after correcting for multiple comparisons, the homozygous rs30187 risk allele genotype (TT) increased disease susceptibility in  HLA-B*51  carriers in epistasis analysis, and the rs30187 TT recessive genotype showed a significant association with risk of cardiac involvement in the all patients and articular involvements in  HLA-B*51  positive patients. 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.

Epistatic Interaction of ERAP1 and HLA-B*51 in Iranian Patients with Behçet’s Disease