RESEARCH - A single nucleotide polymorphism in the IRF5 promoter region is associated wit susceptibility to RA in the Japanese population

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ls of the Rheumatic Diseases 2009;68:377-383

CLINICAL AND EPIDEMIOLOGICAL RESEARCH

A single nucleotide polymorphism in the IRF5 promoter region is

associated with susceptibility to rheumatoid arthritis in the Japanese

population

K Shimane1,2, Y Kochi2, R Yamada3, Y Okada3, A Suzuki2, A Miyatake4, M

Kubo5, Y Nakamura6 and K Yamamoto1

1 Department of Allergy and Rheumatology, Graduate School of Medicine,

the University of Tokyo, Tokyo, Japan

2 Laboratory for Rheumatic Diseases, SRC, RIKEN, Yokohama, Japan

3 Laboratory of Functional Genomics, the Institute of Medical Science,

the University of Tokyo, Tokyo, Japan

4 Miyatake Asthma Clinic, Osaka, Japan

5 Laboratory for Genotyping, SRC, RIKEN, Yokohama, Japan

6 Laboratory of Molecular Medicine, the Institute of Medical Science,

the University of Tokyo, Tokyo, Japan

Objectives: Interferon regulatory factor 5 (IRF5) is a member of the

IRF family of transcription factors, which regulate the production of

proinflammatory cytokines. Polymorphisms in the IRF5 gene have been

associated with susceptibility to systemic lupus erythaematosus (SLE)

in Caucasian and Asian populations, but their involvement in other

autoimmune diseases is still uncertain. Here, we assessed the genetic

role of IRF5 in susceptibility to rheumatoid arthritis (RA) in

Japanese subjects.

Methods: We selected 13 single nucleotide polymorphisms (SNPs) and a

CGGGG insertion–deletion polymorphism in the IRF5 gene. We performed 2

sets of case–control comparisons using Japanese subjects (first set:

830 patients with RA and 658 controls; second set: 1112 patients with

RA and 940 controls), and then performed a stratified analysis using

human leukocyte antigen (HLA)-DRB1 shared epitope (SE) status. We

genotyped the SNPs using TaqMan assays.

Results: A significant association of the rs729302 A allele with RA

susceptibility was found in both sets (odds ratio (OR) 1.22, 95% CI

1.09 to 1.35, p<0.001 in the combined analysis). When the patients

were stratified by the SE, the rs729302 A allele was found to confer

increased risk to RA in patients that were SE negative (OR 1.50, 95%

CI 1.17 to 1.92, p = 0.001) as compared with patients carrying the SE

(OR 1.11, 95% CI 0.93 to 1.33, p = 0.24). In both sets, no genotyped

polymorphisms were significantly associated with RA susceptibility,

but rs729302 was significantly associated.

Conclusions: These findings indicate that the promoter polymorphism of

IRF5 is a genetic factor conferring predisposition to RA, and that it

contributes considerably to disease pathogenesis in patients that were

SE negative.

http://ard.bmj.com/cgi/content/abstract/68/3/377?etoc

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