Association of interferon regulatory factor 5 haplotypes, similar to that found in systemic lupus erythematosus, in a large subgroup of patients with rheumatoid arthritis

被引：81

作者：

Dieguez-Gonzalez, Rebeca ^{[1
]}

Calaza, Manuel ^{[1
]}

Perez-Pampin, Eva ^{[1
]}

Rodriguez de la Serna, Arturo ^{[2
]}

Fernandez-Gutierrez, Benjamin ^{[3
]}

Castaneda, Santos ^{[4
]}

Largo, Raquel ^{[5
]}

Joven, Beatriz ^{[6
]}

Narvaz, Javier ^{[7
]}

Navarro, Federico ^{[8
]}

Luis Marenco, Jose ^{[9
]}

Luis Vicario, Jose ^{[10
]}

Blanco, Francisco J. ^{[11
]}

Carlos Fernandez-Lopez, Jesus ^{[11
]}

Caliz, Rafael ^{[12
]}

Dolores Collado-Escobar, Maria ^{[12
]}

Carreno, Luis ^{[13
]}

Lopez-Longo, Javier ^{[13
]}

Canete, Juan D. ^{[14
,15
]}

Gomez-Reino, Juan J. ^{[16
]}

Gonzalez, Antonio ^{[1
]}

机构：

[1] Univ Santiago, Lab Invest 2, Hosp Clin, Santiago De Compostela 15706, Spain

[2] Hosp Santa Creu & Sant Pau, E-08025 Barcelona, Spain

[3] Hosp Clin San Carlos, Madrid, Spain

[4] Hosp Univ Princesa, Madrid, Spain

[5] Fdn Jimenez Diaz, Madrid, Spain

[6] Hosp 12 Octubre, E-28041 Madrid, Spain

[7] Hosp Univ Bellvitge, Barcelona, Spain

[8] Hosp Univ Virgen Macarena, Seville, Spain

[9] Hosp Univ Valme, Seville, Spain

[10] Reg Transfus Ctr, Madrid, Spain

[11] Hosp Univ Juan Canalejo, Coruna, Spain

[12] Hosp Univ Virgen Nieves, Granada, Spain

[13] Hosp Univ Gregorio Maranon, Madrid, Spain

[14] Hosp Clin Barcelona, Barcelona, Spain

[15] Inst Invest Biomed August Pi & Sunyer, Barcelona, Spain

[16] Hosp Clin Univ de Santiago, Santiago De Compostela, Spain

来源：

ARTHRITIS AND RHEUMATISM | 2008年 / 58卷 / 05期

关键词：

D O I：

10.1002/art.23426

中图分类号：

R5 [内科学];

学科分类号：

1002 [临床医学]; 100201 [内科学];

摘要：

Objective. Previous studies have shown either a lack of effect of IRF5 polymorphisms or an association of the IRF5 gene in only a minor subset of rheumatoid arthritis (RA) patients in whom anti-citrullinated protein antibodies (ACPAs) are absent. The present study was undertaken to investigate the role of genetic variation in IRF5 in susceptibility to RA. Methods. Nine IRF5 single-nucleotide polymorphisms (SNPs) were studied in 1,338 patients with RA and 1,342 control subjects in analyses of exploratory and replication sample collections, with stratification according to sex and by the presence or absence of ACPAs, rheumatoid factor, the shared epitope, the 620W PTPN22 allele, and erosions. A meta-analysis that included results from previous studies was also carried out. Results. Our findings together with those from previous studies, in a total of 4,620 RA patients and 3,741 controls, showed a significant association of the rs2004640 IRF5 SNP in RA patients as a whole (odds ratio [OR] 0.88, 95% confidence interval [95% CI] 0.83-0.94; P = 6.5 x 10(-5) versus controls). This association was stronger in ACPA- patients, but was also present in ACPA+ patients (from 3 sample collections). Further analysis of our exploratory sample collection showed that only patients in the ACPA+ and SE- group lacked an association with IRF5 SNPs. All of the remaining RA patients (ACPA- or SE+) showed a strong association with IRF5 SNPs, which followed a complex pattern of opposing effects mediated by independent haplotypes. The susceptibility haplotype showed an OR of 1.8 (95% CI 1.4-23; P = 1.2 x 10(-6) versus controls), whereas the protective haplotype showed an OR of 0.76 (95% CI 0.6-0.98; P = 0.046 versus controls). Conclusion. IRF5 polymorphisms seem to influence RA susceptibility in a large subgroup of patients, following a pattern of association very similar to that described in patients with systemic lupus erythematosus.

引用

页码：1264 / +

页数：11

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