PLD4 as a novel susceptibility gene for systemic sclerosis in a Japanese population

Chikashi Terao, Koichiro Ohmura, Yasushi Kawaguchi, Tetsuya Nishimoto, Aya Kawasaki, Kazuhiko Takehara, Hiroshi Furukawa, Yuta Kochi, Yuko Ota, Katsunori Ikari, Shinichi Sato, Shigeto Tohma, Ryo Yamada, Kazuhiko Yamamoto, Michiaki Kubo, Hisashi Yamanaka, Masataka Kuwana, Naoyuki Tsuchiya, Fumihiko Matsuda, Tsuneyo Mimori

研究成果: Article

34 引用 (Scopus)

抄録

Objective Systemic sclerosis (SSc) is an autoimmune disease for which multiple susceptibility genes have been reported. Genome-wide association studies have shown that large numbers of susceptibility genes are shared among autoimmune diseases. Recently, our group identified 9 novel susceptibility genes associated with rheumatoid arthritis (RA) in a Japanese population. The aim of this study was to elucidate whether the 18 genes that displayed associations or suggestive associations for RA in our previous study are associated with SSc in Japanese. Methods We performed an association study that included 415 patients with SSc and 16,891 control subjects, followed by a replication study that included 315 patients and 21,054 control subjects. The 18 markers reported to display association with RA were analyzed for their associations with SSc in the first study, and 5 markers were further analyzed in the replication study. The inverse variance method was used to evaluate the associations of these markers with SSc in a combined study. Results In the phospholipase D4 gene (PLD4), rs2841277 displayed a significant association with SSc in Japanese patients (P = 0.00017). We observed that rs2841280 in exon 2 of PLD4 was in strong linkage disequilibrium with rs2841277 and introduced an amino acid alteration. We also observed associations between SSc and rs6932056 in TNFAIP3 and rs2280381 in IRF8 (P = 0.0000095 and P = 0.0030, respectively), both of which displayed associations with SSc in a European population. Conclusion We determined that PLD4 is a novel susceptibility gene for SSc in Japanese, thus confirming the involvement of PLD4 in autoimmunity. Associations between SSc and TNFAIP3 or IRF8 were also detected in our Japanese population. SSc and RA appear to share relatively large proportions of their genetic backgrounds.

元の言語English
ページ(範囲)472-480
ページ数9
ジャーナルArthritis and Rheumatism
65
発行部数2
DOI
出版物ステータスPublished - 01-02-2013

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Phospholipases
Systemic Scleroderma
Population
Genes
Rheumatoid Arthritis
Autoimmune Diseases
Genome-Wide Association Study
Linkage Disequilibrium
Autoimmunity
Exons
Amino Acids

All Science Journal Classification (ASJC) codes

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

これを引用

Terao, C., Ohmura, K., Kawaguchi, Y., Nishimoto, T., Kawasaki, A., Takehara, K., ... Mimori, T. (2013). PLD4 as a novel susceptibility gene for systemic sclerosis in a Japanese population. Arthritis and Rheumatism, 65(2), 472-480. https://doi.org/10.1002/art.37777
Terao, Chikashi ; Ohmura, Koichiro ; Kawaguchi, Yasushi ; Nishimoto, Tetsuya ; Kawasaki, Aya ; Takehara, Kazuhiko ; Furukawa, Hiroshi ; Kochi, Yuta ; Ota, Yuko ; Ikari, Katsunori ; Sato, Shinichi ; Tohma, Shigeto ; Yamada, Ryo ; Yamamoto, Kazuhiko ; Kubo, Michiaki ; Yamanaka, Hisashi ; Kuwana, Masataka ; Tsuchiya, Naoyuki ; Matsuda, Fumihiko ; Mimori, Tsuneyo. / PLD4 as a novel susceptibility gene for systemic sclerosis in a Japanese population. :: Arthritis and Rheumatism. 2013 ; 巻 65, 番号 2. pp. 472-480.
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title = "PLD4 as a novel susceptibility gene for systemic sclerosis in a Japanese population",
abstract = "Objective Systemic sclerosis (SSc) is an autoimmune disease for which multiple susceptibility genes have been reported. Genome-wide association studies have shown that large numbers of susceptibility genes are shared among autoimmune diseases. Recently, our group identified 9 novel susceptibility genes associated with rheumatoid arthritis (RA) in a Japanese population. The aim of this study was to elucidate whether the 18 genes that displayed associations or suggestive associations for RA in our previous study are associated with SSc in Japanese. Methods We performed an association study that included 415 patients with SSc and 16,891 control subjects, followed by a replication study that included 315 patients and 21,054 control subjects. The 18 markers reported to display association with RA were analyzed for their associations with SSc in the first study, and 5 markers were further analyzed in the replication study. The inverse variance method was used to evaluate the associations of these markers with SSc in a combined study. Results In the phospholipase D4 gene (PLD4), rs2841277 displayed a significant association with SSc in Japanese patients (P = 0.00017). We observed that rs2841280 in exon 2 of PLD4 was in strong linkage disequilibrium with rs2841277 and introduced an amino acid alteration. We also observed associations between SSc and rs6932056 in TNFAIP3 and rs2280381 in IRF8 (P = 0.0000095 and P = 0.0030, respectively), both of which displayed associations with SSc in a European population. Conclusion We determined that PLD4 is a novel susceptibility gene for SSc in Japanese, thus confirming the involvement of PLD4 in autoimmunity. Associations between SSc and TNFAIP3 or IRF8 were also detected in our Japanese population. SSc and RA appear to share relatively large proportions of their genetic backgrounds.",
author = "Chikashi Terao and Koichiro Ohmura and Yasushi Kawaguchi and Tetsuya Nishimoto and Aya Kawasaki and Kazuhiko Takehara and Hiroshi Furukawa and Yuta Kochi and Yuko Ota and Katsunori Ikari and Shinichi Sato and Shigeto Tohma and Ryo Yamada and Kazuhiko Yamamoto and Michiaki Kubo and Hisashi Yamanaka and Masataka Kuwana and Naoyuki Tsuchiya and Fumihiko Matsuda and Tsuneyo Mimori",
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Terao, C, Ohmura, K, Kawaguchi, Y, Nishimoto, T, Kawasaki, A, Takehara, K, Furukawa, H, Kochi, Y, Ota, Y, Ikari, K, Sato, S, Tohma, S, Yamada, R, Yamamoto, K, Kubo, M, Yamanaka, H, Kuwana, M, Tsuchiya, N, Matsuda, F & Mimori, T 2013, 'PLD4 as a novel susceptibility gene for systemic sclerosis in a Japanese population', Arthritis and Rheumatism, 巻. 65, 番号 2, pp. 472-480. https://doi.org/10.1002/art.37777

PLD4 as a novel susceptibility gene for systemic sclerosis in a Japanese population. / Terao, Chikashi; Ohmura, Koichiro; Kawaguchi, Yasushi; Nishimoto, Tetsuya; Kawasaki, Aya; Takehara, Kazuhiko; Furukawa, Hiroshi; Kochi, Yuta; Ota, Yuko; Ikari, Katsunori; Sato, Shinichi; Tohma, Shigeto; Yamada, Ryo; Yamamoto, Kazuhiko; Kubo, Michiaki; Yamanaka, Hisashi; Kuwana, Masataka; Tsuchiya, Naoyuki; Matsuda, Fumihiko; Mimori, Tsuneyo.

:: Arthritis and Rheumatism, 巻 65, 番号 2, 01.02.2013, p. 472-480.

研究成果: Article

TY - JOUR

T1 - PLD4 as a novel susceptibility gene for systemic sclerosis in a Japanese population

AU - Terao, Chikashi

AU - Ohmura, Koichiro

AU - Kawaguchi, Yasushi

AU - Nishimoto, Tetsuya

AU - Kawasaki, Aya

AU - Takehara, Kazuhiko

AU - Furukawa, Hiroshi

AU - Kochi, Yuta

AU - Ota, Yuko

AU - Ikari, Katsunori

AU - Sato, Shinichi

AU - Tohma, Shigeto

AU - Yamada, Ryo

AU - Yamamoto, Kazuhiko

AU - Kubo, Michiaki

AU - Yamanaka, Hisashi

AU - Kuwana, Masataka

AU - Tsuchiya, Naoyuki

AU - Matsuda, Fumihiko

AU - Mimori, Tsuneyo

PY - 2013/2/1

Y1 - 2013/2/1

N2 - Objective Systemic sclerosis (SSc) is an autoimmune disease for which multiple susceptibility genes have been reported. Genome-wide association studies have shown that large numbers of susceptibility genes are shared among autoimmune diseases. Recently, our group identified 9 novel susceptibility genes associated with rheumatoid arthritis (RA) in a Japanese population. The aim of this study was to elucidate whether the 18 genes that displayed associations or suggestive associations for RA in our previous study are associated with SSc in Japanese. Methods We performed an association study that included 415 patients with SSc and 16,891 control subjects, followed by a replication study that included 315 patients and 21,054 control subjects. The 18 markers reported to display association with RA were analyzed for their associations with SSc in the first study, and 5 markers were further analyzed in the replication study. The inverse variance method was used to evaluate the associations of these markers with SSc in a combined study. Results In the phospholipase D4 gene (PLD4), rs2841277 displayed a significant association with SSc in Japanese patients (P = 0.00017). We observed that rs2841280 in exon 2 of PLD4 was in strong linkage disequilibrium with rs2841277 and introduced an amino acid alteration. We also observed associations between SSc and rs6932056 in TNFAIP3 and rs2280381 in IRF8 (P = 0.0000095 and P = 0.0030, respectively), both of which displayed associations with SSc in a European population. Conclusion We determined that PLD4 is a novel susceptibility gene for SSc in Japanese, thus confirming the involvement of PLD4 in autoimmunity. Associations between SSc and TNFAIP3 or IRF8 were also detected in our Japanese population. SSc and RA appear to share relatively large proportions of their genetic backgrounds.

AB - Objective Systemic sclerosis (SSc) is an autoimmune disease for which multiple susceptibility genes have been reported. Genome-wide association studies have shown that large numbers of susceptibility genes are shared among autoimmune diseases. Recently, our group identified 9 novel susceptibility genes associated with rheumatoid arthritis (RA) in a Japanese population. The aim of this study was to elucidate whether the 18 genes that displayed associations or suggestive associations for RA in our previous study are associated with SSc in Japanese. Methods We performed an association study that included 415 patients with SSc and 16,891 control subjects, followed by a replication study that included 315 patients and 21,054 control subjects. The 18 markers reported to display association with RA were analyzed for their associations with SSc in the first study, and 5 markers were further analyzed in the replication study. The inverse variance method was used to evaluate the associations of these markers with SSc in a combined study. Results In the phospholipase D4 gene (PLD4), rs2841277 displayed a significant association with SSc in Japanese patients (P = 0.00017). We observed that rs2841280 in exon 2 of PLD4 was in strong linkage disequilibrium with rs2841277 and introduced an amino acid alteration. We also observed associations between SSc and rs6932056 in TNFAIP3 and rs2280381 in IRF8 (P = 0.0000095 and P = 0.0030, respectively), both of which displayed associations with SSc in a European population. Conclusion We determined that PLD4 is a novel susceptibility gene for SSc in Japanese, thus confirming the involvement of PLD4 in autoimmunity. Associations between SSc and TNFAIP3 or IRF8 were also detected in our Japanese population. SSc and RA appear to share relatively large proportions of their genetic backgrounds.

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Terao C, Ohmura K, Kawaguchi Y, Nishimoto T, Kawasaki A, Takehara K その他. PLD4 as a novel susceptibility gene for systemic sclerosis in a Japanese population. Arthritis and Rheumatism. 2013 2 1;65(2):472-480. https://doi.org/10.1002/art.37777