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

Pimentel-Santos, F. M., Ligeiro, D., Matos, M., Mourão, A. F., Sousa, E., Pinto, P., Ribeiro, A., Sousa, M., Barcelos, A., Godinho, F., Cruz, M., Fonseca, J. E., Guedes-Pinto, H., Trindade, H., Evans, D. M., Brown, M.A., Branco, J. C., Alves De Matos, A., Ribeiro, C., Pimentão, J. B., Mateus, M., Nero, P., Araújo, P., Barros, R., Falcão, S., Pinto, T. L., Castelão, W., Caetano-Lopes, J., Silva, C., Simões, E., Madeira, H., Santos, H., Patto, J. V., Ferreira, J., Micaelo, M., Mediavilla, M. J., Branco, P. S., Canas Da Silva, J., Garcês, S., Tavares, V., Araújo, D., Costa, J. A., Costa, L., Afonso, M. C., Bogas, M., Alcino, S., Cunha, I., Redondo, J., Cravo, A. R., Sequeira, G., Santos, R. A., & Carvalho, M. E. (2009) Association of IL23R and ERAP1 genes with ankylosing spondylitis in a Portuguese population. Clinical and Experimental Rheumatology, 27(5), pp. 800-806.

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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.


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.


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.


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.

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ID Code: 87992
Item Type: Journal Article
Refereed: Yes
Additional Information: No file attached.
Keywords: Ankylosing spondylitis, ERAP1, IL23R, adult, allele, article, Bath Ankylosing Spondylitis Disease Activity, clinical feature, controlled study, disease activity, ERAP1 gene, ethnic group, female, gene, gene locus, genetic association, genetic marker, genetic susceptibility, genetic variability, genotype, high risk patient, human, IL23R gene, major clinical study, male, Metrology and Functional Indices, modified Stoke Ankylosing Spondylitis Spinal Score, North America, onset age, Portugal, priority journal, quantitative analysis, rating scale, single nucleotide polymorphism, symptom, United Kingdom, Aminopeptidases, Case-Control Studies, Gene Frequency, Humans, Middle Aged, Odds Ratio, Polymorphism, Single Nucleotide, Receptors, Interleukin, Severity of Illness Index, Spondylitis, Ankylosing
ISSN: 0392-856X
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 01 Oct 2015 23:19
Last Modified: 22 Aug 2016 23:43

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