Association of IL23R and ERAP1 genes with ankylosing spondylitis in a Portuguese population

Fernando M. Pimentel-Santos, Dario Ligeiro, Mafalda Matos, Ana F. Mourão, Elsa Sousa, Patricia Pinto, Ana Ribeiro, Miguel Sousa, Anabela Barcelos, Fatima Godinho, Margarida Cruz, Joao E. Fonseca, Henrique Guedes-Pinto, Helder Trindade, David M. Evans, Matthew A. Brown, Jaime C. Branco, António Alves De Matos, Célia Ribeiro, José Bravo PimentãoMargarida Mateus, Patricia Nero, Paula Araújo, Rita Barros, Sandra Falcão, Teresa Laura Pinto, Walter Castelão, Joana Caetano-Lopes, Cândida Silva, Eugénia Simões, Helena Madeira, Helena Santos, José Vaz Patto, Julia Ferreira, Manuela Micaelo, Maria Jesus Mediavilla, Pedro Soares Branco, José Canas Da Silva, Sandra Garcês, Viviana Tavares, Domingos Araújo, José A. Costa, Lúcia Costa, Maria Carmo Afonso, Mónica Bogas, Sergio Alcino, Inês Cunha, José Redondo, Ana Rita Cravo, Graça Sequeira, Rui André Santos, M. Elisabete Carvalho

Research output: Contribution to journalArticlepeer-review

82 Citations (Scopus)

Abstract

Objective: Association between ankylosing spondylitis (AS) and two genes, ERAP1 and IL23R, has recently been reported in North American and British populations. The population attributable risk fraction for ERAP1 in this study was 25%, and for IL23R, 9%. Confirmation of these findings to ERAP1 in other ethnic groups has not yet been demonstrated. We sought to test the association between single nucleotide polymorphisms (SNPs) in these genes and susceptibility to AS among a Portuguese population. We also investigated the role of these genes in clinical manifestations of AS, including age of symptom onset, the Bath Ankylosing Spondylitis Disease Activity, Metrology and Functional Indices, and the modified Stoke Ankylosing Spondylitis Spinal Score. Methods: The study was conducted on 358 AS cases and 285 ethnically matched Portuguese healthy controls. AS was defined according to the modified New York Criteria. Genotyping of IL23R and ERAP1 allelic variants was carried out with TaqMan allelic discrimination assays. Association analysis was performed using the Cochrane-Armitage and linear regression tests of genotypes as implemented in PLINK for dichotomous and quantitative variables respectively. A meta-analysis for Portuguese and previously published Spanish IL23R data was performed using the StatsDirect® Statistical tools, by fixed and random effects models. Results: A total of 14 nsSNPs markers (8 for IL23R, 5 for ERAPl, 1 for LN-PEP) were analysed. Three markers (2 for IL23R and 1 for ERAP1) showed significant single-locus disease associations, confirming that the association of these genes with AS in the Portuguese population. The strongest associated SNP in IL23R was rs1004819 (OR=1.4, p=0.0049), and in ERAP1 was rs30187 (OR=1.26, p=0.035). The population attributable risk fractions in the Portuguese population for these SNPs are 11% and 9.7% respectively. No association was seen with any SNP in LN-PEP, which flanks ERAP1 and was associated with AS in the British population. No association was seen with clinical manifestations of AS. Conclusions: These results show that IL23R and ERAP1 genes are also associated with susceptibility to AS in the Portuguese population, and that they contribute a significant proportion of the population risk for this disease.

Original languageEnglish
Pages (from-to)800-806
Number of pages7
JournalClinical and Experimental Rheumatology
Volume27
Issue number5
Publication statusPublished - 2009
Externally publishedYes

Keywords

  • Ankylosing spondylitis
  • ERAP1
  • IL23R

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