title: Protective effect of an ERAP1 haplotype in ankylosing spondylitis: investigating non-MHC genes in HLA-B27-positive individuals.
abstract: OBJECTIVE
  The association of non-MHC genes with AS has been recently suggested. We aimed to investigate the association of the ERAP1, IL23R and TNFSF15 regions and the susceptibility to and protection from AS in HLA-B27-positive individuals.
  
  
  METHODS
  A total of 200 unrelated AS patients and 559 healthy unrelated subjects, all HLA-B27 positive, were tested. Twenty single nucleotide polymorphisms (SNPs) were investigated in and near IL23R (nine SNPs), in ERAP1 (five SNPs) and in TNFSF15 (six SNPs).
  
  
  RESULTS
  ERAP1 rs30187 [odds ratio (OR) = 1.5, P = 4.7 × 10(-3)] had the strongest association with AS susceptibility. A protective effect was found in three of the ERAP1 SNPs: rs17482078 (OR = 0.7, P = 2.8 × 10(-2)), rs10050860 (OR = 0.7, P = 2.3 × 10(-2)), rs2287987 (OR = 0.6, P = 1.3 × 10(-2)). The ERAP1 haplotype rs17482078/rs10050860/rs30187/rs2287987-CCTT showed an association with AS susceptibility (P = 6.8 × 10(-3)) and a protective effect was identified in rs17482078/rs10050860/rs30187/rs2287987-TTCC (P = 3.1 × 10(-2)). Significant association with AS susceptibility was found in one IL23R marker (rs1004819, P = 4.3 × 10(-2), OR = 1.3). No associations were observed in the TNFSF15 region.
  
  
  CONCLUSIONS
  The identification of a new protection haplotype in ERAP1 and the lack of association of the TNFSF15 region can provide new insights into the understanding of the mechanisms underlying the susceptibility to and protection from AS.
authors.affiliation: SEEBMO, Hospital de Santo Espirito da ilha Terceira, Canada do Breado, 9700 Angra do Heroísmo, Portugal. bfbettencourt@seebmo.org.
authors.forename: Bruno Filipe
authors.initials: BF
authors.lastname: Bettencourt
authors.forename: Fabiana Leal
authors.initials: FL
authors.lastname: Rocha
authors.forename: Helena
authors.initials: H
authors.lastname: Alves
authors.forename: Rosa
authors.initials: R
authors.lastname: Amorim
authors.forename: Joana
authors.initials: J
authors.lastname: Caetano-Lopes
authors.forename: Elsa
authors.initials: E
authors.lastname: Vieira-Sousa
authors.forename: Fernando
authors.initials: F
authors.lastname: Pimentel-Santos
authors.forename: Manuela
authors.initials: M
authors.lastname: Lima
authors.forename: Graça
authors.initials: G
authors.lastname: Porto
authors.forename: Jaime C
authors.initials: JC
authors.lastname: Branco
authors.forename: João Eurico
authors.initials: JE
authors.lastname: Fonseca
authors.forename: Jácome
authors.initials: J
authors.lastname: Bruges-Armas
mesh_terms: D000328:Adult; D000368:Aged; D000626:Aminopeptidases / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D015796:HLA-B27 Antigen / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018123:Receptors, Interleukin / Q000235:genetics*; D013167:Spondylitis, Ankylosing / Q000235:genetics*; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000235:genetics*
chemical_list: D015796:HLA-B27 Antigen; C515500:IL23R protein, human; D015778:Minor Histocompatibility Antigens; D018123:Receptors, Interleukin; C117026:TNFSF15 protein, human; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15; D000626:Aminopeptidases; C464841:ERAP1 protein, human
keywords: ERAP1; IL23R; TNFSF15; ankylosing spondylitis; protection haplotype