AB0016 Interferon Regulatory Factor 5 (IRF5) Gene Variant Rs2004640 is Associated with Carotid Intimal Medial Thickness in Rheumatoid Arthritis Patients

Objective.Two interferon regulatory factor 5 (IRF5) gene variants were examined for association with rheumatoid arthritis (RA).Methods.A total of 2300 patients with RA and 1836 controls were recruited from 2 independent RA studies in Sweden. One insertion-deletion polymorphism (CGGGG indel) and one single-nucleotide polymorphism (rs10488631) in the IRF5 gene were genotyped and analyzed within RA subgroups stratified by rheumatoid factor (RF) and anticitrullinated peptide antibodies (ACPA).Results.The CGGGG indel was preferentially associated with the RF-negative (OR 1.29, p = 7.9 × 10−5) and ACPA-negative (OR 1.27, p = 7.3 × 10−5) RA subgroups compared to the seropositive counterparts. rs10488631 was exclusively associated within the seronegative RA subgroups (RF-negative: OR 1.24, p = 0.016; ACPA-negative: OR 1.27, p = 4.1 × 10−3).Conclusion.Both the CGGGG indel and rs10488631 are relevant for RA susceptibility, especially for seronegative RA.

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

Arthritis & Rheumatism ◽

10.1002/art.23426 ◽

2008 ◽

Vol 58 (5) ◽

pp. 1264-1274 ◽

Cited By ~ 62

Author(s):

Rebeca Dieguez-Gonzalez ◽

Manuel Calaza ◽

Eva Perez-Pampin ◽

Arturo Rodriguez de la Serna ◽

Benjamin Fernandez-Gutierrez ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Interferon Regulatory Factor ◽

Regulatory Factor ◽

Systemic Lupus ◽

Interferon Regulatory Factor 5 ◽

Large Subgroup

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Putative Role of Functional Interferon Regulatory Factor 5 (IRF5) Polymorphism in Rheumatoid Arthritis in a Korean Population

The Journal of Rheumatology ◽

10.3899/jrheum.080114 ◽

2008 ◽

Vol 35 (11) ◽

pp. 2106-2112 ◽

Cited By ~ 15

Author(s):

YUN JUNG KIM ◽

JEONG HA PARK ◽

IL KIM ◽

JI ON KIM ◽

JOON SEOL BAE ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Lupus Erythematosus ◽

Interferon Regulatory Factor ◽

Genetic Effects ◽

Korean Population ◽

Separate Analysis ◽

Regulatory Factor ◽

Interferon Regulatory Factor 5 ◽

Increased Risk ◽

Se Status

ObjectiveRecent studies suggest that polymorphisms of interferon regulatory factor 5 (IRF5) are significantly associated with systemic lupus erythematosus in several populations. The effect of IRF5 polymorphism on susceptibility to rheumatoid arthritis (RA) has been investigated, and the results were inconsistent. We analyzed the genetic effects of IRF5 polymorphisms on RA in a Korean population.MethodsEight single-nucleotide polymorphisms (SNP) and 2 insertion-deletion polymorphisms in IRF5 were genotyped in 2183 subjects (1204 RA cases and 979 controls) using the TaqMan® method. The genetic effects of SNP on the risk of RA were evaluated using chi-square tests and multivariate logistic regression, controlling for age, sex, and shared epitope (SE), and we then performed conditional analysis by SE status and anti-cyclic citrullinated peptide (anti-CCP) antibody (Ab) status. Data from a Mantel-Haenszel metaanalysis of odds ratios (OR) were subsequently combined in a separate analysis with the results of the association of rs2004640 with RA from a previous study.ResultsTwo of the IRF5 polymorphisms, CGGGGindel (OR 1.38, 95% CI 1.09–1.76, pcorr = 0.04) and rs2004640 (OR 1.36, 95% CI 1.09–1.68, pcorr = 0.03), and one haplotype, including the rs2004640 and the CGGGGindel, ht3 (A-Del-T-C-del-A-T) (OR 1.39, 95% CI 1.09–1.79, pcorr = 0.04) were significantly associated with an increased risk of RA. After stratification according to anti-CCPAb and SE status, rs2004640 SNP was associated with the anti-CCPAb-positive (OR 1.47, 95% CI 1.15–1.88, pcorr = 0.01) or SE-positive group (OR 1.54, 95% CI 1.14–2.09, pcorr = 0.03). A combined analysis including all 3 independent cohorts from the previous study revealed an association of the rs2004640 with RA (pooled OR 1.21, 95% CI 1.07–1.38, pooled p = 0.0031 in dominant model).ConclusionOur results suggest that the IRF5 polymorphism is associated with genetic susceptibility to RA at least in a Korean population, and that it may contribute to disease susceptibility in SE-positive or anti-CCP Ab-positive patients with RA.

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Interferon regulatory factor 5 genetic variants are associated with cardiovascular disease in patients with rheumatoid arthritis

Arthritis Research & Therapy ◽

10.1186/ar4608 ◽

2014 ◽

Vol 16 (4) ◽

pp. R146 ◽

Cited By ~ 14

Author(s):

Mercedes García-Bermúdez ◽

Raquel López-Mejías ◽

Fernanda Genre ◽

Santos Castañeda ◽

Javier Llorca ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Cardiovascular Disease ◽

Genetic Variants ◽

Interferon Regulatory Factor ◽

Regulatory Factor ◽

Interferon Regulatory Factor 5

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The interferon regulatory factor 5 gene confers susceptibility to rheumatoid arthritis and influences its erosive phenotype

Annals of the Rheumatic Diseases ◽

10.1136/ard.2010.129171 ◽

2010 ◽

Vol 70 (1) ◽

pp. 117-121 ◽

Cited By ~ 35

Author(s):

K. Dawidowicz ◽

Y. Allanore ◽

M. Guedj ◽

C. Pierlot ◽

S. Bombardieri ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Interferon Regulatory Factor ◽

Regulatory Factor ◽

Interferon Regulatory Factor 5

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Association of Polymorphisms in Interferon Regulatory Factor 5 Gene with Rheumatoid Arthritis: A Metaanalysis

The Journal of Rheumatology ◽

10.3899/jrheum.081054 ◽

2009 ◽

Vol 36 (4) ◽

pp. 693-697 ◽

Cited By ~ 21

Author(s):

SEUNG WOO HAN ◽

WON KI LEE ◽

KI TAE KWON ◽

BYUNG KI LEE ◽

EON JEONG NAM ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Interferon Regulatory Factor ◽

Nucleotide Polymorphisms ◽

Regulatory Factor ◽

Case Control Studies ◽

Single Nucleotide ◽

Funnel Plot ◽

Interferon Regulatory Factor 5 ◽

Regression Test

Objective.We investigated potential associations between rheumatoid arthritis (RA) and interferon regulatory factor 5 (IRF5) polymorphisms in a metaanalysis.Methods.This metaanalysis included 5 case-control studies, which provided a total of 6582 RA cases and 5375 controls. Odds ratios (OR) were employed to evaluate the risk of RA according to the 4 single-nucleotide polymorphisms (SNP) inIRF5(rs729302, rs2004640, rs752637, and rs2280714) and data were analyzed in respect to association between alleles.Results.Among 4 candidate SNP, rs729302, rs2004640, and rs2280714 were statistically significant; both allele C of rs729302 and allele G of rs2004640 within the promoter region ofIRF5were associated with a protective effect [random-effects (RE) OR 0.889, 95% confidence interval (CI) 0.803–0.977, p = 0.015 for rs729302; and RE OR 0.905, 95% CI 0.848–0.965, p = 0.002 for rs2004640]. Similar results were also obtained in T allele of rs2280714 in the 3’-untranslated region (RE OR 0.927, 95% CI 0.866–0.992, p = 0.029). There was no evidence of publication bias from funnel-plot asymmetry and Egger’s regression test.Conclusion.Our metaanalysis supported the evidence of the significant role ofIRF5polymorphisms in RA.

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