The association of a nonsynonymous single-nucleotide polymorphism in TNFAIP3 with systemic lupus erythematosus and rheumatoid arthritis in the Japanese population.

Abstract

OBJECTIVE:

Genome-wide association (GWA) studies in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in Caucasian populations have independently identified risk variants in and near the tumor necrosis factor alpha (TNFalpha)-induced protein 3 gene (TNFAIP3), which is crucial for the regulation of TNF-mediated signaling and Toll-like receptor signaling. The aim of this study was to assess the role of TNFAIP3 in the development of SLE and RA in Japanese subjects.

METHODS:

We selected 2 single-nucleotide polymorphisms (SNPs) from previous GWA studies. Rs2230926 is a nonsynonymous SNP in TNFAIP3 and is associated with SLE, while rs10499194 is an intergenic SNP associated with RA. We then performed 2 independent sets of SLE case-control comparisons (717 patients and 1,362 control subjects) and 3 sets of RA case-control comparisons (3,446 patients and 2,344 control subjects) using Japanese subjects. We genotyped SNPs using TaqMan assays.

RESULTS:

We observed a significant association between rs2230926 and an increased risk of SLE and RA in the Japanese population (for SLE, odds ratio [OR] 1.92, 95% confidence interval [95% CI] 1.53-2.41, P = 1.9 x 10(-8); for RA, OR 1.35, 95% CI 1.18-1.56, P = 2.6 x 10(-5)). The intergenic SNP rs10499194 was also associated with SLE and RA, while the risk allele for RA in Caucasians was protective against the diseases in our population.

CONCLUSION:

We demonstrated a significant association between the nonsynonymous variant in TNFAIP3 and the risk for SLE and RA in the Japanese population. TNFAIP3, similar to STAT4 and IRF5, may be a common genetic risk factor for SLE and RA that is shared between the Caucasian and Japanese populations.

• Authors: Kenichi Shimane, Yuta Kochi, Tetsuya Horita, Katsunori Ikari, Hirofumi Amano, Michito Hirakata, Akiko Okamoto, Ryo Yamada, Keiko Myouzen, Akari Suzuki, Michiaki Kubo, Tatsuya Atsumi, Takao Koike, Yoshinari Takasaki, Shigeki Momohara, Hisashi Yamanaka, Yusuke Nakamura, Kazuhiko Yamamoto
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 62 Issue 2 Pg. 574-9 (Feb 2010) ISSN: 0004-3591 [Print] United States
• PMID: 20112363 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA-Binding Proteins
• Intracellular Signaling Peptides and Proteins
• Nuclear Proteins
• TNFAIP3 protein, human
• Tumor Necrosis Factor alpha-Induced Protein 3

Topics

• Adult
• Arthritis, Rheumatoid (ethnology, genetics)
• Asian People (genetics, statistics & numerical data)
• Case-Control Studies
• DNA-Binding Proteins
• Female
• Genome-Wide Association Study
• Genotype
• Humans
• Intracellular Signaling Peptides and Proteins (genetics)
• Japan (epidemiology)
• Linkage Disequilibrium
• Lupus Erythematosus, Systemic (ethnology, genetics)
• Male
• Middle Aged
• Nuclear Proteins (genetics)
• Polymorphism, Single Nucleotide
• Risk Factors
• Tumor Necrosis Factor alpha-Induced Protein 3