Variations in ORAI1 gene associated with kawasaki disease

Yoshihiro Onouchi, Ryuji Fukazawa, Kenichiro Yamamura, Hiroyuki Suzuki, Nobuyuki Kakimoto, Tomohiro Suenaga, Takashi Takeuchi, Hiromichi Hamada, Takafumi Honda, Kumi Yasukawa, Masaru Terai, Ryota Ebata, Kouji Higashi, Tsutomu Saji, Yasushi Kemmotsu, Shinichi Takatsuki, Kazunobu Ouchi, Fumio Kishi, Tetsushi Yoshikawa, Toshiro NagaiKunihiro Hamamoto, Yoshitake Sato, Akihito Honda, Hironobu Kobayashi, Junichi Sato, Shoichi Shibuta, Masakazu Miyawaki, Ko Oishi, Hironobu Yamaga, Noriyuki Aoyagi, Megumi Yoshiyama, Ritsuko Miyashita, Yuji Murata, Akihiro Fujino, Kouichi Ozaki, Tomisaku Kawasaki, Jun Abe, Mitsuru Seki, Tohru Kobayashi, Hirokazu Arakawa, Shunichi Ogawa, Toshiro Hara, Akira Hata, Toshihiro Tanaka

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Kawasaki disease (KD; MIM#61175) is a systemic vasculitis syndrome with unknown etiology which predominantly affects infants and children. Recent findings of susceptibility genes for KD suggest possible involvement of the Ca2+/NFAT pathway in the pathogenesis of KD. ORAI1 is a Ca2+ release activated Ca2+ (CRAC) channel mediating store-operated Ca2+ entry (SOCE) on the plasma membrane. The gene for ORAI1 is located in chromosome 12q24 where a positive linkage signal was observed in our previous affected sib-pair study of KD. A common non-synonymous single nucleotide polymorphism located within exon 2 of ORAI1 (rs3741596) was significantly associated with KD (P = 0.028 in the discovery sample set (729 KD cases and 1,315 controls), P = 0.0056 in the replication sample set (1,813 KD cases vs. 1,097 controls) and P = 0.00041 in a meta-Analysis by the Mantel-Haenszel method). Interestingly, frequency of the risk allele of rs3741596 is more than 20 times higher in Japanese compared to Europeans. We also found a rare 6 base-pair inframe insertion variant associated with KD (rs141919534; 2,544 KD cases vs. 2,414 controls, P = 0.012). These data indicate that ORAI1 gene variations are associated with KD and may suggest the potential importance of the Ca2+/NFAT pathway in the pathogenesis of this disorder.

Original languageEnglish
Article numbere0145486
JournalPloS one
Volume11
Issue number1
DOIs
Publication statusPublished - 01-01-2016

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Mucocutaneous Lymph Node Syndrome
Genes
calcium
Systemic Vasculitis
genes
Cell membranes
Chromosomes
Polymorphism
Gene Frequency
Base Pairing
pathogenesis
Single Nucleotide Polymorphism
Meta-Analysis
Exons
Nucleotides
vasculitis
Cell Membrane
meta-analysis
single nucleotide polymorphism
exons

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Onouchi, Y., Fukazawa, R., Yamamura, K., Suzuki, H., Kakimoto, N., Suenaga, T., ... Tanaka, T. (2016). Variations in ORAI1 gene associated with kawasaki disease. PloS one, 11(1), [e0145486]. https://doi.org/10.1371/journal.pone.0145486
Onouchi, Yoshihiro ; Fukazawa, Ryuji ; Yamamura, Kenichiro ; Suzuki, Hiroyuki ; Kakimoto, Nobuyuki ; Suenaga, Tomohiro ; Takeuchi, Takashi ; Hamada, Hiromichi ; Honda, Takafumi ; Yasukawa, Kumi ; Terai, Masaru ; Ebata, Ryota ; Higashi, Kouji ; Saji, Tsutomu ; Kemmotsu, Yasushi ; Takatsuki, Shinichi ; Ouchi, Kazunobu ; Kishi, Fumio ; Yoshikawa, Tetsushi ; Nagai, Toshiro ; Hamamoto, Kunihiro ; Sato, Yoshitake ; Honda, Akihito ; Kobayashi, Hironobu ; Sato, Junichi ; Shibuta, Shoichi ; Miyawaki, Masakazu ; Oishi, Ko ; Yamaga, Hironobu ; Aoyagi, Noriyuki ; Yoshiyama, Megumi ; Miyashita, Ritsuko ; Murata, Yuji ; Fujino, Akihiro ; Ozaki, Kouichi ; Kawasaki, Tomisaku ; Abe, Jun ; Seki, Mitsuru ; Kobayashi, Tohru ; Arakawa, Hirokazu ; Ogawa, Shunichi ; Hara, Toshiro ; Hata, Akira ; Tanaka, Toshihiro. / Variations in ORAI1 gene associated with kawasaki disease. In: PloS one. 2016 ; Vol. 11, No. 1.
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abstract = "Kawasaki disease (KD; MIM#61175) is a systemic vasculitis syndrome with unknown etiology which predominantly affects infants and children. Recent findings of susceptibility genes for KD suggest possible involvement of the Ca2+/NFAT pathway in the pathogenesis of KD. ORAI1 is a Ca2+ release activated Ca2+ (CRAC) channel mediating store-operated Ca2+ entry (SOCE) on the plasma membrane. The gene for ORAI1 is located in chromosome 12q24 where a positive linkage signal was observed in our previous affected sib-pair study of KD. A common non-synonymous single nucleotide polymorphism located within exon 2 of ORAI1 (rs3741596) was significantly associated with KD (P = 0.028 in the discovery sample set (729 KD cases and 1,315 controls), P = 0.0056 in the replication sample set (1,813 KD cases vs. 1,097 controls) and P = 0.00041 in a meta-Analysis by the Mantel-Haenszel method). Interestingly, frequency of the risk allele of rs3741596 is more than 20 times higher in Japanese compared to Europeans. We also found a rare 6 base-pair inframe insertion variant associated with KD (rs141919534; 2,544 KD cases vs. 2,414 controls, P = 0.012). These data indicate that ORAI1 gene variations are associated with KD and may suggest the potential importance of the Ca2+/NFAT pathway in the pathogenesis of this disorder.",
author = "Yoshihiro Onouchi and Ryuji Fukazawa and Kenichiro Yamamura and Hiroyuki Suzuki and Nobuyuki Kakimoto and Tomohiro Suenaga and Takashi Takeuchi and Hiromichi Hamada and Takafumi Honda and Kumi Yasukawa and Masaru Terai and Ryota Ebata and Kouji Higashi and Tsutomu Saji and Yasushi Kemmotsu and Shinichi Takatsuki and Kazunobu Ouchi and Fumio Kishi and Tetsushi Yoshikawa and Toshiro Nagai and Kunihiro Hamamoto and Yoshitake Sato and Akihito Honda and Hironobu Kobayashi and Junichi Sato and Shoichi Shibuta and Masakazu Miyawaki and Ko Oishi and Hironobu Yamaga and Noriyuki Aoyagi and Megumi Yoshiyama and Ritsuko Miyashita and Yuji Murata and Akihiro Fujino and Kouichi Ozaki and Tomisaku Kawasaki and Jun Abe and Mitsuru Seki and Tohru Kobayashi and Hirokazu Arakawa and Shunichi Ogawa and Toshiro Hara and Akira Hata and Toshihiro Tanaka",
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Onouchi, Y, Fukazawa, R, Yamamura, K, Suzuki, H, Kakimoto, N, Suenaga, T, Takeuchi, T, Hamada, H, Honda, T, Yasukawa, K, Terai, M, Ebata, R, Higashi, K, Saji, T, Kemmotsu, Y, Takatsuki, S, Ouchi, K, Kishi, F, Yoshikawa, T, Nagai, T, Hamamoto, K, Sato, Y, Honda, A, Kobayashi, H, Sato, J, Shibuta, S, Miyawaki, M, Oishi, K, Yamaga, H, Aoyagi, N, Yoshiyama, M, Miyashita, R, Murata, Y, Fujino, A, Ozaki, K, Kawasaki, T, Abe, J, Seki, M, Kobayashi, T, Arakawa, H, Ogawa, S, Hara, T, Hata, A & Tanaka, T 2016, 'Variations in ORAI1 gene associated with kawasaki disease', PloS one, vol. 11, no. 1, e0145486. https://doi.org/10.1371/journal.pone.0145486

Variations in ORAI1 gene associated with kawasaki disease. / Onouchi, Yoshihiro; Fukazawa, Ryuji; Yamamura, Kenichiro; Suzuki, Hiroyuki; Kakimoto, Nobuyuki; Suenaga, Tomohiro; Takeuchi, Takashi; Hamada, Hiromichi; Honda, Takafumi; Yasukawa, Kumi; Terai, Masaru; Ebata, Ryota; Higashi, Kouji; Saji, Tsutomu; Kemmotsu, Yasushi; Takatsuki, Shinichi; Ouchi, Kazunobu; Kishi, Fumio; Yoshikawa, Tetsushi; Nagai, Toshiro; Hamamoto, Kunihiro; Sato, Yoshitake; Honda, Akihito; Kobayashi, Hironobu; Sato, Junichi; Shibuta, Shoichi; Miyawaki, Masakazu; Oishi, Ko; Yamaga, Hironobu; Aoyagi, Noriyuki; Yoshiyama, Megumi; Miyashita, Ritsuko; Murata, Yuji; Fujino, Akihiro; Ozaki, Kouichi; Kawasaki, Tomisaku; Abe, Jun; Seki, Mitsuru; Kobayashi, Tohru; Arakawa, Hirokazu; Ogawa, Shunichi; Hara, Toshiro; Hata, Akira; Tanaka, Toshihiro.

In: PloS one, Vol. 11, No. 1, e0145486, 01.01.2016.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Variations in ORAI1 gene associated with kawasaki disease

AU - Onouchi, Yoshihiro

AU - Fukazawa, Ryuji

AU - Yamamura, Kenichiro

AU - Suzuki, Hiroyuki

AU - Kakimoto, Nobuyuki

AU - Suenaga, Tomohiro

AU - Takeuchi, Takashi

AU - Hamada, Hiromichi

AU - Honda, Takafumi

AU - Yasukawa, Kumi

AU - Terai, Masaru

AU - Ebata, Ryota

AU - Higashi, Kouji

AU - Saji, Tsutomu

AU - Kemmotsu, Yasushi

AU - Takatsuki, Shinichi

AU - Ouchi, Kazunobu

AU - Kishi, Fumio

AU - Yoshikawa, Tetsushi

AU - Nagai, Toshiro

AU - Hamamoto, Kunihiro

AU - Sato, Yoshitake

AU - Honda, Akihito

AU - Kobayashi, Hironobu

AU - Sato, Junichi

AU - Shibuta, Shoichi

AU - Miyawaki, Masakazu

AU - Oishi, Ko

AU - Yamaga, Hironobu

AU - Aoyagi, Noriyuki

AU - Yoshiyama, Megumi

AU - Miyashita, Ritsuko

AU - Murata, Yuji

AU - Fujino, Akihiro

AU - Ozaki, Kouichi

AU - Kawasaki, Tomisaku

AU - Abe, Jun

AU - Seki, Mitsuru

AU - Kobayashi, Tohru

AU - Arakawa, Hirokazu

AU - Ogawa, Shunichi

AU - Hara, Toshiro

AU - Hata, Akira

AU - Tanaka, Toshihiro

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Kawasaki disease (KD; MIM#61175) is a systemic vasculitis syndrome with unknown etiology which predominantly affects infants and children. Recent findings of susceptibility genes for KD suggest possible involvement of the Ca2+/NFAT pathway in the pathogenesis of KD. ORAI1 is a Ca2+ release activated Ca2+ (CRAC) channel mediating store-operated Ca2+ entry (SOCE) on the plasma membrane. The gene for ORAI1 is located in chromosome 12q24 where a positive linkage signal was observed in our previous affected sib-pair study of KD. A common non-synonymous single nucleotide polymorphism located within exon 2 of ORAI1 (rs3741596) was significantly associated with KD (P = 0.028 in the discovery sample set (729 KD cases and 1,315 controls), P = 0.0056 in the replication sample set (1,813 KD cases vs. 1,097 controls) and P = 0.00041 in a meta-Analysis by the Mantel-Haenszel method). Interestingly, frequency of the risk allele of rs3741596 is more than 20 times higher in Japanese compared to Europeans. We also found a rare 6 base-pair inframe insertion variant associated with KD (rs141919534; 2,544 KD cases vs. 2,414 controls, P = 0.012). These data indicate that ORAI1 gene variations are associated with KD and may suggest the potential importance of the Ca2+/NFAT pathway in the pathogenesis of this disorder.

AB - Kawasaki disease (KD; MIM#61175) is a systemic vasculitis syndrome with unknown etiology which predominantly affects infants and children. Recent findings of susceptibility genes for KD suggest possible involvement of the Ca2+/NFAT pathway in the pathogenesis of KD. ORAI1 is a Ca2+ release activated Ca2+ (CRAC) channel mediating store-operated Ca2+ entry (SOCE) on the plasma membrane. The gene for ORAI1 is located in chromosome 12q24 where a positive linkage signal was observed in our previous affected sib-pair study of KD. A common non-synonymous single nucleotide polymorphism located within exon 2 of ORAI1 (rs3741596) was significantly associated with KD (P = 0.028 in the discovery sample set (729 KD cases and 1,315 controls), P = 0.0056 in the replication sample set (1,813 KD cases vs. 1,097 controls) and P = 0.00041 in a meta-Analysis by the Mantel-Haenszel method). Interestingly, frequency of the risk allele of rs3741596 is more than 20 times higher in Japanese compared to Europeans. We also found a rare 6 base-pair inframe insertion variant associated with KD (rs141919534; 2,544 KD cases vs. 2,414 controls, P = 0.012). These data indicate that ORAI1 gene variations are associated with KD and may suggest the potential importance of the Ca2+/NFAT pathway in the pathogenesis of this disorder.

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Onouchi Y, Fukazawa R, Yamamura K, Suzuki H, Kakimoto N, Suenaga T et al. Variations in ORAI1 gene associated with kawasaki disease. PloS one. 2016 Jan 1;11(1). e0145486. https://doi.org/10.1371/journal.pone.0145486