This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
Abstract
Objective
Recent 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.
Methods
Eight 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.
Results
Two 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).
Conclusion
Our 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.
Key Indexing Terms:Footnotes
-
Y.J. Kim, MD, Instructor; J.H. Park, MD, Instructor; I. Kim, MD, Instructor, Division of Rheumatology, Department of Internal Medicine, Hanyang University College of Medicine and the Hospital for Rheumatic Diseases, Hanyang University; J.O. Kim; J.S. Bae, PhD, Department of Genetic Epidemiology, SNP Genetics, Inc.; H.D. Shin, PhD, Laboratory of Genomic Diversity, Department of Life Science, Sogang University; S-C. Bae, MD, PhD, MPH, Professor, Division of Rheumatology, Department of Internal Medicine, Hanyang University College of Medicine, Director, the Hospital for Rheumatic Diseases, Hanyang University.
-
Supported in part by a grant of the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (01-PJ3-PG6-01GN11- 0002).
- Accepted for publication July 10, 2008.
Log in using your username and password
Purchase access
In this issue
