A single nucleotide polymorphism in the IRF5 promoter region is associated with susceptibility to rheumatoid arthritis in the Japanese population

K. Shimane, Y. Kochi, R. Yamada, Y. Okada, A. Suzuki, A. Miyatake, Michiaki Kubo, Y. Nakamura, K. Yamamoto

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

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% Cl 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% Cl 1.17 to 1.92, p = 0.001) as compared with patients carrying the SE (OR 1.11, 95% Cl 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.

Original languageEnglish
Pages (from-to)377-383
Number of pages7
JournalAnnals of the Rheumatic Diseases
Volume68
Issue number3
DOIs
Publication statusPublished - 01-03-2009
Externally publishedYes

Fingerprint

Interferon Regulatory Factors
Polymorphism
Genetic Promoter Regions
Single Nucleotide Polymorphism
Rheumatoid Arthritis
Nucleotides
Epitopes
Population
Odds Ratio
Genes
Alleles
HLA Antigens
Assays
Systemic Lupus Erythematosus
Transcription Factors
Autoimmune Diseases
Association reactions
Cytokines

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Shimane, K. ; Kochi, Y. ; Yamada, R. ; Okada, Y. ; Suzuki, A. ; Miyatake, A. ; Kubo, Michiaki ; Nakamura, Y. ; Yamamoto, K. / A single nucleotide polymorphism in the IRF5 promoter region is associated with susceptibility to rheumatoid arthritis in the Japanese population. In: Annals of the Rheumatic Diseases. 2009 ; Vol. 68, No. 3. pp. 377-383.
@article{497f12a379024387820c32689ce2c55a,
title = "A single nucleotide polymorphism in the IRF5 promoter region is associated with susceptibility to rheumatoid arthritis in the Japanese population",
abstract = "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{\%} Cl 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{\%} Cl 1.17 to 1.92, p = 0.001) as compared with patients carrying the SE (OR 1.11, 95{\%} Cl 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.",
author = "K. Shimane and Y. Kochi and R. Yamada and Y. Okada and A. Suzuki and A. Miyatake and Michiaki Kubo and Y. Nakamura and K. Yamamoto",
year = "2009",
month = "3",
day = "1",
doi = "10.1136/ard.2007.085704",
language = "English",
volume = "68",
pages = "377--383",
journal = "Annals of the Rheumatic Diseases",
issn = "0003-4967",
publisher = "BMJ Publishing Group",
number = "3",

}

A single nucleotide polymorphism in the IRF5 promoter region is associated with susceptibility to rheumatoid arthritis in the Japanese population. / Shimane, K.; Kochi, Y.; Yamada, R.; Okada, Y.; Suzuki, A.; Miyatake, A.; Kubo, Michiaki; Nakamura, Y.; Yamamoto, K.

In: Annals of the Rheumatic Diseases, Vol. 68, No. 3, 01.03.2009, p. 377-383.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A single nucleotide polymorphism in the IRF5 promoter region is associated with susceptibility to rheumatoid arthritis in the Japanese population

AU - Shimane, K.

AU - Kochi, Y.

AU - Yamada, R.

AU - Okada, Y.

AU - Suzuki, A.

AU - Miyatake, A.

AU - Kubo, Michiaki

AU - Nakamura, Y.

AU - Yamamoto, K.

PY - 2009/3/1

Y1 - 2009/3/1

N2 - 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% Cl 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% Cl 1.17 to 1.92, p = 0.001) as compared with patients carrying the SE (OR 1.11, 95% Cl 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.

AB - 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% Cl 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% Cl 1.17 to 1.92, p = 0.001) as compared with patients carrying the SE (OR 1.11, 95% Cl 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.

UR - http://www.scopus.com/inward/record.url?scp=61449134184&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=61449134184&partnerID=8YFLogxK

U2 - 10.1136/ard.2007.085704

DO - 10.1136/ard.2007.085704

M3 - Article

C2 - 18408250

AN - SCOPUS:61449134184

VL - 68

SP - 377

EP - 383

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

SN - 0003-4967

IS - 3

ER -