Association of STAT4 with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in the Japanese population

Shu Kobayashi, Katsunori Ikari, Hirotaka Kaneko, Yuta Kochi, Kazuhiko Yamamoto, Kenichi Shimane, Yusuke Nakamura, Yoshiaki Toyama, Takeshi Mochizuki, So Tsukahara, Yasushi Kawaguchi, Chihiro Terai, Masako Hara, Taisuke Tomatsu, Hisashi Yamanaka, Takahiko Horiuchi, Kayoko Tao, Koji Yasutomo, Daisuke Hamada, Natsuo Yasui & 5 others Hiroshi Inoue, Mitsuo Itakura, Hiroshi Okamoto, Naoyuki Kamatani, Shigeki Momohara

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Abstract

Objective. STAT4 encodes a transcriptional factor that transmits signals induced by several key cytokines, and it might be a key molecule in the development of autoimmune diseases. Recently, a STAT4 haplotype was reported to be associated with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in Caucasian populations. This was replicated in a Korean RA population. Interestingly, the degree of risk of RA susceptibility with the STAT4 haplotype was similar in the Caucasian and Korean populations. The present study was undertaken to investigate the effect of STAT4 on susceptibility to RA and SLE in the Japanese. Methods. We performed an association study using 3 independent Japanese RA case-control populations (total 3,567 cases and 2,199 controls) and 3 independent Japanese SLE populations (total 591 cases). All samples were genotyped using the TaqMan fluorogenic 5′ nuclease assay for single-nucleotide polymorphism (SNP) rs7574865, which tags the susceptibility haplotype. The association of the SNP with disease susceptibility in each case-control study was calculated using Fisher's exact test, and the results were combined, using the Mantel-Haenszel method, to obtain combined odds ratios (ORs). Results. We observed a significant association of the STAT4 polymorphism with susceptibility to both RA and SLE. The combined ORs for RA and SLE, respectively, were 1.27 (P = 8.4 × 10-9) and 1.61 (P = 2.1 × 10-11) for allele frequency distribution; these ORs were quite similar to those previously observed in the Caucasian population. Conclusion. We conclude that STAT4 is associated with RA and SLE in the Japanese. Our results indicate that STAT4 is a common genetic risk factor for autoimmune diseases, with similar strength across major racial groups.

Original languageEnglish
Pages (from-to)1940-1946
Number of pages7
JournalArthritis and rheumatism
Volume58
Issue number7
DOIs
Publication statusPublished - Jul 1 2008

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Systemic Lupus Erythematosus
Rheumatoid Arthritis
Population
Haplotypes
Odds Ratio
Autoimmune Diseases
Single Nucleotide Polymorphism
Disease Susceptibility
Gene Frequency
Case-Control Studies
Cytokines

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

Cite this

Kobayashi, S., Ikari, K., Kaneko, H., Kochi, Y., Yamamoto, K., Shimane, K., ... Momohara, S. (2008). Association of STAT4 with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in the Japanese population. Arthritis and rheumatism, 58(7), 1940-1946. https://doi.org/10.1002/art.23494

Association of STAT4 with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in the Japanese population. / Kobayashi, Shu; Ikari, Katsunori; Kaneko, Hirotaka; Kochi, Yuta; Yamamoto, Kazuhiko; Shimane, Kenichi; Nakamura, Yusuke; Toyama, Yoshiaki; Mochizuki, Takeshi; Tsukahara, So; Kawaguchi, Yasushi; Terai, Chihiro; Hara, Masako; Tomatsu, Taisuke; Yamanaka, Hisashi; Horiuchi, Takahiko; Tao, Kayoko; Yasutomo, Koji; Hamada, Daisuke; Yasui, Natsuo; Inoue, Hiroshi; Itakura, Mitsuo; Okamoto, Hiroshi; Kamatani, Naoyuki; Momohara, Shigeki.

In: Arthritis and rheumatism, Vol. 58, No. 7, 01.07.2008, p. 1940-1946.

Research output: Contribution to journalArticle

Kobayashi, S, Ikari, K, Kaneko, H, Kochi, Y, Yamamoto, K, Shimane, K, Nakamura, Y, Toyama, Y, Mochizuki, T, Tsukahara, S, Kawaguchi, Y, Terai, C, Hara, M, Tomatsu, T, Yamanaka, H, Horiuchi, T, Tao, K, Yasutomo, K, Hamada, D, Yasui, N, Inoue, H, Itakura, M, Okamoto, H, Kamatani, N & Momohara, S 2008, 'Association of STAT4 with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in the Japanese population', Arthritis and rheumatism, vol. 58, no. 7, pp. 1940-1946. https://doi.org/10.1002/art.23494
Kobayashi, Shu ; Ikari, Katsunori ; Kaneko, Hirotaka ; Kochi, Yuta ; Yamamoto, Kazuhiko ; Shimane, Kenichi ; Nakamura, Yusuke ; Toyama, Yoshiaki ; Mochizuki, Takeshi ; Tsukahara, So ; Kawaguchi, Yasushi ; Terai, Chihiro ; Hara, Masako ; Tomatsu, Taisuke ; Yamanaka, Hisashi ; Horiuchi, Takahiko ; Tao, Kayoko ; Yasutomo, Koji ; Hamada, Daisuke ; Yasui, Natsuo ; Inoue, Hiroshi ; Itakura, Mitsuo ; Okamoto, Hiroshi ; Kamatani, Naoyuki ; Momohara, Shigeki. / Association of STAT4 with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in the Japanese population. In: Arthritis and rheumatism. 2008 ; Vol. 58, No. 7. pp. 1940-1946.
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abstract = "Objective. STAT4 encodes a transcriptional factor that transmits signals induced by several key cytokines, and it might be a key molecule in the development of autoimmune diseases. Recently, a STAT4 haplotype was reported to be associated with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in Caucasian populations. This was replicated in a Korean RA population. Interestingly, the degree of risk of RA susceptibility with the STAT4 haplotype was similar in the Caucasian and Korean populations. The present study was undertaken to investigate the effect of STAT4 on susceptibility to RA and SLE in the Japanese. Methods. We performed an association study using 3 independent Japanese RA case-control populations (total 3,567 cases and 2,199 controls) and 3 independent Japanese SLE populations (total 591 cases). All samples were genotyped using the TaqMan fluorogenic 5′ nuclease assay for single-nucleotide polymorphism (SNP) rs7574865, which tags the susceptibility haplotype. The association of the SNP with disease susceptibility in each case-control study was calculated using Fisher's exact test, and the results were combined, using the Mantel-Haenszel method, to obtain combined odds ratios (ORs). Results. We observed a significant association of the STAT4 polymorphism with susceptibility to both RA and SLE. The combined ORs for RA and SLE, respectively, were 1.27 (P = 8.4 × 10-9) and 1.61 (P = 2.1 × 10-11) for allele frequency distribution; these ORs were quite similar to those previously observed in the Caucasian population. Conclusion. We conclude that STAT4 is associated with RA and SLE in the Japanese. Our results indicate that STAT4 is a common genetic risk factor for autoimmune diseases, with similar strength across major racial groups.",
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AU - Kobayashi, Shu

AU - Ikari, Katsunori

AU - Kaneko, Hirotaka

AU - Kochi, Yuta

AU - Yamamoto, Kazuhiko

AU - Shimane, Kenichi

AU - Nakamura, Yusuke

AU - Toyama, Yoshiaki

AU - Mochizuki, Takeshi

AU - Tsukahara, So

AU - Kawaguchi, Yasushi

AU - Terai, Chihiro

AU - Hara, Masako

AU - Tomatsu, Taisuke

AU - Yamanaka, Hisashi

AU - Horiuchi, Takahiko

AU - Tao, Kayoko

AU - Yasutomo, Koji

AU - Hamada, Daisuke

AU - Yasui, Natsuo

AU - Inoue, Hiroshi

AU - Itakura, Mitsuo

AU - Okamoto, Hiroshi

AU - Kamatani, Naoyuki

AU - Momohara, Shigeki

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N2 - Objective. STAT4 encodes a transcriptional factor that transmits signals induced by several key cytokines, and it might be a key molecule in the development of autoimmune diseases. Recently, a STAT4 haplotype was reported to be associated with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in Caucasian populations. This was replicated in a Korean RA population. Interestingly, the degree of risk of RA susceptibility with the STAT4 haplotype was similar in the Caucasian and Korean populations. The present study was undertaken to investigate the effect of STAT4 on susceptibility to RA and SLE in the Japanese. Methods. We performed an association study using 3 independent Japanese RA case-control populations (total 3,567 cases and 2,199 controls) and 3 independent Japanese SLE populations (total 591 cases). All samples were genotyped using the TaqMan fluorogenic 5′ nuclease assay for single-nucleotide polymorphism (SNP) rs7574865, which tags the susceptibility haplotype. The association of the SNP with disease susceptibility in each case-control study was calculated using Fisher's exact test, and the results were combined, using the Mantel-Haenszel method, to obtain combined odds ratios (ORs). Results. We observed a significant association of the STAT4 polymorphism with susceptibility to both RA and SLE. The combined ORs for RA and SLE, respectively, were 1.27 (P = 8.4 × 10-9) and 1.61 (P = 2.1 × 10-11) for allele frequency distribution; these ORs were quite similar to those previously observed in the Caucasian population. Conclusion. We conclude that STAT4 is associated with RA and SLE in the Japanese. Our results indicate that STAT4 is a common genetic risk factor for autoimmune diseases, with similar strength across major racial groups.

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