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

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.