A hypoactive endoplasmic reticulum aminopeptidase-1 (ERAP1) allotype contributes to the risk of Behçet’s disease by inefficiently producing disease-protective peptides, according to research published in the Annals of Rheumatic Disease.
Elaine F Remmers, PhD, of the Inflammatory Disease Section of the National Human Genome Research Institute in Bethesda, Maryland and colleagues conducted a study of 1900 cases of Behçet’s disease and 1779 unrelated controls. The researchers determined ERAP1 protein allotypes and their contribution to Behçet’s disease risk via haplotype identification and disease association analyses.
One ERAP1 protein allotype with 5 non-ancestral amino acids was found to be recessively associated with the disease. “The ERAP1 association was absent in individuals who lacked HLA-B*51,” the authors wrote. “Individuals who carry HLA-B*51 and who are also homozygous for the haplotype had an increased disease odds compared with those with neither risk factor.”
Summary & Clinical Applicability
“This association … only influenced disease risk in individuals who also carried the Behçet’s disease-associated HLA type, HLA-B*51,” the authors noted. “Individuals who are also homozygous for Hap10 have a nearly 11-fold increased disease odds compared with individuals with neither genetic risk factor.”
“Thus, the ERAP1 Hap10 allotype could either inefficiently produce disease-protective peptides by failing to trip precursor peptides, or alternatively it could fail to digest/destroy disease-promoting peptides,” the authors concluded. “Identifying the nature and source of such peptides … would be an important step towards elucidating the mechanism by which HLA-B*51 contributes to Behçet’s disease risk.”
Takeuchi M, Ombrello MJ, Kirino Y, et al. A single edoplasmic reticulum aminopeptidase-1 protein allotype is a strong risk factor for Behçeet’s disease in HLA-B*51 carriers. Ann Rheum Dis. 2016;0:1-4; doi: 10.1136/annrheumdis-2015-209059.