Item type |
学術雑誌論文 / Journal Article(1) |
公開日 |
2013-07-08 |
タイトル |
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タイトル |
A Nonsynonymous Polymorphism in Semaphorin 3A as a Risk Factor for Human Unexplained Cardiac Arrest with Documented Ventricular Fibrillation |
言語 |
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言語 |
eng |
資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
著者 |
Nakano, Yukiko
Chayama, Kazuaki
Ochi, Hidenori
Toshishige, Masaaki
Hayashida, Yasufumi
Miki, Daiki
Hayes, C. Nelson
Suzuki, Hidekazu
Tokuyama, Takehito
Oda, Noboru
Suenari, Kazuyoshi
Uchimura-Makita, Yuko
Kajihara, Kenta
Sairaku, Akinori
Motoda, Chikaaki
Fujiwara, Mai
Watanabe, Yoshikazu
Yoshida, Yukihiko
Ohkubo, Kimie
Watanabe, Ichiro
Nogami, Akihiko
Hasegawa, Kanae
Watanabe, Hiroshi
Endo, Naoto
Aiba, Takeshi
Shimizu, Wataru
Ohno, Seiko
Horie, Minoru
Arihiro, Koji
Tashiro, Satoshi
Makita, Naomasa
Kihara, Yasuki
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抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
Unexplained cardiac arrest (UCA) with documented ventricular fibrillation (VF) is a major cause of sudden cardiac death. Abnormal sympathetic innervations have been shown to be a trigger of ventricular fibrillation. Further, adequate expression of SEMA3A was reported to be critical for normal patterning of cardiac sympathetic innervation. We investigated the relevance of the semaphorin 3A (SEMA3A) gene located at chromosome 5 in the etiology of UCA. Eighty-three Japanese patients diagnosed with UCA and 2,958 healthy controls from two different geographic regions in Japan were enrolled. A nonsynonymous polymorphism (I334V, rs138694505A>G) in exon 10 of the SEMA3A gene identified through resequencing was significantly associated with UCA (combined P = 0.0004, OR 3.08, 95%CI 1.67-5.7). Overall, 15.7% of UCA patients carried the risk genotype G, whereas only 5.6% did in controls. In patients with SEMA3AI334V, VF predominantly occurred at rest during the night. They showed sinus bradycardia, and their RR intervals on the 12-lead electrocardiography tended to be longer than those in patients without SEMA3AI334V (1031±111 ms versus 932±182 ms, P = 0.039). Immunofluorescence staining of cardiac biopsy specimens revealed that sympathetic nerves, which are absent in the subendocardial layer in normal hearts, extended to the subendocardial layer only in patients with SEMA3AI334V. Functional analyses revealed that the axon-repelling and axon-collapsing activities of mutant SEMA3AI334V genes were significantly weaker than those of wild-type SEMA3A genes. A high incidence of SEMA3AI334V in UCA patients and inappropriate innervation patterning in their hearts implicate involvement of the SEMA3A gene in the pathogenesis of UCA. |
書誌情報 |
PLoS Genetics
巻 9,
号 4,
p. e1003364,
発行日 2013-04-11
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出版者 |
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出版者 |
Public Library of Science |
EISSN |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
15537404 |
DOI |
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関連タイプ |
isIdenticalTo |
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識別子タイプ |
DOI |
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関連識別子 |
10.1371/journal.pgen.1003364 |
権利 |
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権利情報 |
© 2013 Nakano et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
著者版フラグ |
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出版タイプ |
VoR |
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出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
引用 |
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内容記述タイプ |
Other |
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内容記述 |
PLoS Genetics, 9(4), Article numbere 1003364; 2013 |