Journal
JOURNAL OF RHEUMATOLOGY
Volume 36, Issue 5, Pages 881-886Publisher
J RHEUMATOL PUBL CO
DOI: 10.3899/jrheum.080398
Keywords
PADI4; RHEUMATOID ARTHRITIS; ANTI-CITRULLINATED PROTEIN ANTIBODY; HLA ANTIGENS
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Objective. A functional haplotype of peptidyl arginine deiminase 4 (PADI4) was associated with susceptibility to rheumatoid arthritis (RA) in Asian Populations, but the results are contradictory in Europeans. We investigated (1) the association of 2 single-nucleotide polymorphisms (SNP) located in exon 2 of PADI4 with RA in another Caucasian Population; and (2) the association between PADI4 and anti-citrullinated protein (anti-CCP) antibodies. Methods. DNA samples were obtained from 405 French RA patients and 275 controls. All RA patients met the revised criteria of the American College of Rheumatology. PADI4 89 163(G -> A) and PADI4_90 245(T -> C) SNP were genotyped using a PCR-RFLP method confirmed by direct sequencing. All patients and controls were genotyped for HLA-DRB1. The presence of anti-CCP antibodies was tested in 243 RA patients using in ELISA technique. Results. We focused on PADI4_89 163(G -> A) and PADI4_90 245(T -> C) SNP that distinguished 2 main haplotypes: AC haplotype (PADI4_89*A PADI4_90*C) and GT haplotype (PAD_4-89*G PADI4_90*T), described, respectively, as nonsusceptible and susceptible. A positive association between RA and presence of the GT haplotype was found in the heterozygous state (p = 0.002) and the homozygous state (RA patients 22%, controls 13% p = 0.005). A correlation was observed between the presence but not the level of anti-CCP antibodies and the GT heterozygous (p = 0.03) and homozygous (p = 0.05) haplotypes. No correlation was found between the HLA-DRB1 shared epitope and any of the PADI4 haplotypes. Conclusion. Our findings confirm those of Japanese, Korean, and Canadian studies and Suggest that PADI4 may be a new susceptibility gene independent of HLA-DRB1 for RA in Caucasian populations. (First Release April 1 2009; J Rheumatol 2009;36:881-6; doi: 10.3899/jrheum.080398)
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