title: Endoplasmic reticulum-associated amino-peptidase 1 and rheumatic disease: genetics.
abstract: OBJECTIVE
  This article will review the genetic evidence implicating ERAP1, which encodes the endoplasmic reticulum-associated amino-peptidase 1, in susceptibility to rheumatic disease.
  
  
  RESULTS
  Genetic variants and haplotypes of ERAP1 are associated with AS, psoriasis, and Behçet's disease in people of varying ancestries. In each of these diseases, disease-associated variants of ERAP1 have been shown to interact with disease-associated class I human leukocyte antigen alleles to influence disease risk. Functionally, disease-associated missense variants of ERAP1 concertedly alter ERAP1 enzymatic function, both quantitatively and qualitatively, whereas other disease-associated variants influence ERAP1 expression. Therefore, ERAP1 haplotypes (or allotypes) should be examined as functional units. Biologically, this amounts to an examination of the gene regulation and function of the protein encoded by each allotype. Genetically, the relationship between disease risk and ERAP1 allotypes should be examined to determine whether allotypes or individual variants produce the most parsimonious risk models.
  
  
  CONCLUSIONS
  Future investigations of ERAP1 should focus on comprehensively characterizing naturally occurring ERAP1 allotypes, examining the enzymatic function and gene expression of each allotype, and identifying specific allotypes that influence disease susceptibility.
authors.affiliation: aTranslational Genetics and Genomics Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health bInflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ombrello
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Kastner
authors.forename: Elaine F
authors.initials: EF
authors.lastname: Remmers
mesh_terms: D000626:Aminopeptidases / Q000235:genetics*; D001528:Behcet Syndrome / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D007129:Immunoglobulin Gm Allotypes / Q000235:genetics; D015778:Minor Histocompatibility Antigens; D011565:Psoriasis / Q000235:genetics; D012216:Rheumatic Diseases / Q000235:genetics*; D013167:Spondylitis, Ankylosing / Q000235:genetics
chemical_list: D007129:Immunoglobulin Gm Allotypes; D015778:Minor Histocompatibility Antigens; D000626:Aminopeptidases; C464841:ERAP1 protein, human