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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Adolescent, Adult, Aged, Aminopeptidases, Behcet Syndrome, Case-Control Studies, Female, Genetic Association Studies, Genetic Predisposition to Disease, Genetic Variation, Genotype, HLA-B51 Antigen, Haplotypes, Homozygote, Humans, Male, Middle Aged, Minor Histocompatibility Antigens, Mutation, Missense, Risk Factors, Turkey, Young Adult.
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Is a single endoplasmic reticulum aminopeptidase-1 protein allotype a strong risk factor for Behçet 's disease in HLA-B*51 carriers? Context: 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. 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. One ERAP1 protein allotype with five non-ancestral amino acids was recessively associated with disease (p=3.13×10
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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. Final Decision: yes