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Rheumatology Advance Access published online on July 5, 2005

Rheumatology, doi:10.1093/rheumatology/kei008
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© The Author 2005. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
Received April 4, 2005
Accepted May 24, 2005

Original Papers

PADI4 polymorphisms are not associated with rheumatoid arthritis in the Spanish population

A. Martinez 1*, A. Valdivia 1, D. Pascual-Salcedo 2, J. Ramón Lamas 3, M. Fernández-Arquero 1, A. Balsa 4, B. Fernández-Gutiérrez 3, E. G. de la Concha 1, and E. Urcelay 1

1 Immunology Department, Hospital Clínico San Carlos, Madrid, Spain
2 Immunology Department, Hospital Universitario La Paz, Madrid, Spain
3 Rheumatology Department, Hospital Clínico San Carlos, Madrid, Spain
4 Rheumatology Department, Hospital Universitario La Paz, Madrid, Spain

* To whom correspondence should be addressed.
A. Martinez, E-mail: alfmdoncel{at}terra.es


   Abstract

Objectives. The presence of anti-citrullinated peptide antibodies is the most specific serological marker known of rheumatoid arthritis (RA). The PADI4 gene, encoding a haematopoietic isoform of the peptidylarginine deiminase citrullinating enzyme, has recently been associated with susceptibility to RA in the Japanese population. A subsequent UK report could not confirm this association, and a later French study also yielded a negative result. Given this discrepancy and the importance of antibodies against citrullinated peptides in the early course of the disease, we performed a replication study.

Methods. Three hundred and fifty-four Spanish RA patients and 498 Spanish controls were recruited from two Madrid hospitals. The padi4_104 and padi4_94 single-nucleotide polymorphisms (SNP) were analysed by TaqMan assays.

Results. Similarly to what was described in the British and French population, the less frequent allele of this SNP was not associated with the disease (genotype TT, 16.1% in RA patients vs 14.3% in controls; P = 0.46, odds ratio 1.15, 95% confidence interval 0.78-1.71). A confirmatory negative result was obtained on analysing another SNP in the same gene, padi4_94, in 248 RA patients and 394 controls.

Conclusions. The results of our group and from the British and French studies strongly suggest that polymorphisms of the PADI4 gene do not play a role in susceptibility to RA in European populations.

Keywords: Rheumatoid arthritis; Citrulline; Polymorphism; Peptidylarginine deiminase; Single-nucleotide polymorphism.
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