@article{oai:nagasaki-u.repo.nii.ac.jp:00007770,
 author = {Nakano, Yukiko and Chayama, Kazuaki and Ochi, Hidenori and Toshishige, Masaaki and Hayashida, Yasufumi and Miki, Daiki and Hayes, C. Nelson and Suzuki, Hidekazu and Tokuyama, Takehito and Oda, Noboru and Suenari, Kazuyoshi and Uchimura-Makita, Yuko and Kajihara, Kenta and Sairaku, Akinori and Motoda, Chikaaki and Fujiwara, Mai and Watanabe, Yoshikazu and Yoshida, Yukihiko and Ohkubo, Kimie and Watanabe, Ichiro and Nogami, Akihiko and Hasegawa, Kanae and Watanabe, Hiroshi and Endo, Naoto and Aiba, Takeshi and Shimizu, Wataru and Ohno, Seiko and Horie, Minoru and Arihiro, Koji and Tashiro, Satoshi and Makita, Naomasa and Kihara, Yasuki},
 issue = {4},
 journal = {PLoS Genetics},
 month = {Apr},
 note = {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., PLoS Genetics, 9(4), Article numbere 1003364; 2013},
 title = {A Nonsynonymous Polymorphism in Semaphorin 3A as a Risk Factor for Human Unexplained Cardiac Arrest with Documented Ventricular Fibrillation},
 volume = {9},
 year = {2013}
}