RT Journal Article
SR Electronic
T1 A single endoplasmic reticulum aminopeptidase-1 protein allotype is a strong risk factor for Behçet's disease in HLA-B*51 carriers
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP 2208
OP 2211
DO 10.1136/annrheumdis-2015-209059
VO 75
IS 12
A1 Masaki Takeuchi
A1 Michael J Ombrello
A1 Yohei Kirino
A1 Burak Erer
A1 Ilknur Tugal-Tutkun
A1 Emire Seyahi
A1 Yilmaz Özyazgan
A1 Norman R Watts
A1 Ahmet Gül
A1 Daniel L Kastner
A1 Elaine F Remmers
YR 2016
UL http://ard.bmj.com/content/75/12/2208.abstract
AB Introduction Endoplasmic reticulum aminopeptidase-1 (ERAP1) protein is highly polymorphic with numerous missense amino acid variants. We sought to determine the naturally occurring ERAP1 protein allotypes and their contribution to Behçet's disease.Methods Genotypes of all reported missense ERAP1 gene variants with 1000 Genomes Project EUR superpopulation frequency >1% were determined in 1900 Behçet's disease cases and 1779 controls from Turkey. ERAP1 protein allotypes and their contributions to Behçet's disease risk were determined by haplotype identification and disease association analyses.Results One ERAP1 protein allotype with five non-ancestral amino acids was recessively associated with disease (p=3.13×10−6, OR 2.55, 95% CI 1.70 to 3.82). The ERAP1 association was absent in individuals who lacked HLA-B*51. 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 (p=4.80×10−20, OR 10.96, 95% CI 5.91 to 20.32).Discussion The Behçet's disease-associated ERAP1 protein allotype was previously shown to have poor peptide trimming activity. Combined with its requirement for HLA-B*51, these data suggest that a hypoactive ERAP1 allotype contributes to Behçet's disease risk by altering the peptides available for binding to HLA-B*51.