TY - JOUR
T1 - SCN5A variants in Japanese patients with left ventricular noncompaction and arrhythmia
AU - Shan, Lishen
AU - Makita, Naomasa
AU - Xing, Yanlin
AU - Watanabe, Sayaka
AU - Futatani, Takeshi
AU - Ye, Fei
AU - Saito, Kazuyoshi
AU - Ibuki, Keijiro
AU - Watanabe, Kazuhiro
AU - Hirono, Keiichi
AU - Uese, Keiichiro
AU - Ichida, Fukiko
AU - Miyawaki, Toshio
AU - Origasa, Hideki
AU - Bowles, Neil E.
AU - Towbin, Jeffrey A.
N1 - Funding Information:
The authors thank to LVNC study collaborators: Teiji Akagi, Hikaru Doi, Hiromichi Hamada, Hidetoshi Hayakawa, Tohru Hioka, Yoshimi Hiraumi, Hitoshi Horigome, Takehiko Ishida, Shiro Ishikawa, Takamitsu Ishikawa, Hiroki Kajino, Mitsuya Kudo, Shunji Kurotobi, Tohru Matsushita, Hiroshi Mito, Toshihiro Mitomori, Masaru Miura, Toshiharu Miyake, Yasuhiro Morikami, Yasuo Murakami, Masao Nakagawa, Tomotaka Nakayama, Koichi Nihei, Masataka Nii, Yasuo Ono, Norio Sakai, Shingo Sakamoto, Hisashi Sugiyama, Mitsuo Takeda, Yasuhiko Tanaka, Hirokazu Taniguchi, Masaru Terai, Hideshi Tomita, Masaki Tsukashita, Takashi Urashima, Yasunobu Wakabayashi, Kenji Yasuda, Muneo Yoshibayashi, and Jun Yoshimoto. Fukiko Ichida is supported by grants from the Ministry of Education, Culture, Sports, Science and Technology in Japan.
PY - 2008/4
Y1 - 2008/4
N2 - Left ventricular noncompaction (LVNC) is a genetically heterogenous disorder. Mutations in the human cardiac sodium channel alpha-subunit gene (SCN5A) are involved in the pathophysiology of cardiac arrhythmias and cardiomyopathies. This study was performed to compare the frequency of SCN5A variants in LVNC patients with or without arrhythmias, and to investigate the relationship between variants and disease severity. DNA was isolated from the peripheral blood of 62 Japanese probands with LVNC, comprising 17 familial cases and 45 sporadic cases. Blood samples were screened for variants in SCN5A using single-strand conformational polymorphism analysis (SSCP) and DNA sequencing. Seven variants, rs6599230:G > A, c.453C > T, c.1141-3C > A, rs1805124:A > G (p.H558R), rs1805125:C > T (p.P1090L), c.3996C > T, and rs1805126:T > C were identified in 7 familial and 12 sporadic cases. The frequency of SCN5A variants was significantly higher in the patients with arrhythmias than those without (50% vs 7%: P = 0.0003), suggesting these variants represent a risk factor for arrhythmia and supporting the hypothesis that genes encoding ion channels are involved in LVNC pathophysiology. The LVNC patients with heart failure also had high occurence of SCN5A variants, suggesting the presence of SCN5A variants and/or arrhythmias increase the severity of LVNC.
AB - Left ventricular noncompaction (LVNC) is a genetically heterogenous disorder. Mutations in the human cardiac sodium channel alpha-subunit gene (SCN5A) are involved in the pathophysiology of cardiac arrhythmias and cardiomyopathies. This study was performed to compare the frequency of SCN5A variants in LVNC patients with or without arrhythmias, and to investigate the relationship between variants and disease severity. DNA was isolated from the peripheral blood of 62 Japanese probands with LVNC, comprising 17 familial cases and 45 sporadic cases. Blood samples were screened for variants in SCN5A using single-strand conformational polymorphism analysis (SSCP) and DNA sequencing. Seven variants, rs6599230:G > A, c.453C > T, c.1141-3C > A, rs1805124:A > G (p.H558R), rs1805125:C > T (p.P1090L), c.3996C > T, and rs1805126:T > C were identified in 7 familial and 12 sporadic cases. The frequency of SCN5A variants was significantly higher in the patients with arrhythmias than those without (50% vs 7%: P = 0.0003), suggesting these variants represent a risk factor for arrhythmia and supporting the hypothesis that genes encoding ion channels are involved in LVNC pathophysiology. The LVNC patients with heart failure also had high occurence of SCN5A variants, suggesting the presence of SCN5A variants and/or arrhythmias increase the severity of LVNC.
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U2 - 10.1016/j.ymgme.2007.10.009
DO - 10.1016/j.ymgme.2007.10.009
M3 - Article
C2 - 18368697
AN - SCOPUS:40749095261
VL - 93
SP - 468
EP - 474
JO - Biochemical Medicine and Metabolic Biology
JF - Biochemical Medicine and Metabolic Biology
SN - 1096-7192
IS - 4
ER -