Putative role of functional interferon regulatory factor 5 (IRF5) polymorphism in rheumatoid arthritis in a Korean population.
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(R) 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-CCP Ab and SE status, rs2004640 SNP was associated with the anti-CCP Ab-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).


CONCLUSIONS
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.
Division of Rheumatology, Department of Internal Medicine, Hanyang University College of Medicine and the Hospital for Rheumatic Diseases, Hanyang University, Seoul, Republic of Korea.
Yun Jung
YJ
Kim
Jeong Ha
JH
Park
Il
I
Kim
Ji On
JO
Kim
Joon Seol
JS
Bae
Hyoung Doo
HD
Shin
Sang-Cheol
SC
Bae
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000208:ethnology* / Q000235:genetics*; D044466:Asian People / Q000235:genetics* / Q000706:statistics & numerical data; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology; D006239:Haplotypes; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics*; D007723:Korea / Q000453:epidemiology; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
C431713:IRF5 protein, human; D050835:Interferon Regulatory Factors