Protective effect of an ERAP1 haplotype in ankylosing spondylitis: investigating non-MHC genes in HLA-B27-positive individuals

Rheumatology (Oxford). 2013 Dec;52(12):2168-76. doi: 10.1093/rheumatology/ket269. Epub 2013 Sep 17.

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.

Conclusion: 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.

Keywords: ERAP1; IL23R; TNFSF15; ankylosing spondylitis; protection haplotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aminopeptidases / genetics*
  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • HLA-B27 Antigen / genetics
  • Haplotypes
  • Humans
  • Linkage Disequilibrium / genetics
  • Male
  • Middle Aged
  • Minor Histocompatibility Antigens
  • Polymorphism, Single Nucleotide / genetics*
  • Receptors, Interleukin / genetics*
  • Spondylitis, Ankylosing / genetics*
  • Tumor Necrosis Factor Ligand Superfamily Member 15 / genetics*

Substances

  • HLA-B27 Antigen
  • IL23R protein, human
  • Minor Histocompatibility Antigens
  • Receptors, Interleukin
  • TNFSF15 protein, human
  • Tumor Necrosis Factor Ligand Superfamily Member 15
  • Aminopeptidases
  • ERAP1 protein, human