PADI4 polymorphisms are not associated with rheumatoid arthritis in the Spanish population.
OBJECTIVE
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.
Martinez
A
A
Immunology Department, Hospital Clinico San Carlos, C/Martín Lagos, s/n, 28040 Madrid, Spain. alfmdoncel@terra.es
Valdivia
A
A
Pascual-Salcedo
D
D
Lamas
J Ramón
JR
Fernández-Arquero
M
M
Balsa
A
A
Fernández-Gutiérrez
B
B
de la Concha
E G
EG
Urcelay
E
E
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D002956:Citrulline / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D006867:Hydrolases / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases
D002956:Citrulline; D006867:Hydrolases; C000629235:PADI4 protein, human; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases