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Association between Genetic Polymorphisms in Ca(v)2.3 (R-type) Ca2+ Channels and Fentanyl Sensitivity in Patients Undergoing Painful Cosmetic Surgery

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タイトル: Association between Genetic Polymorphisms in Ca(v)2.3 (R-type) Ca2+ Channels and Fentanyl Sensitivity in Patients Undergoing Painful Cosmetic Surgery
著者: Ide, Soichiro 著作を一覧する
Nishizawa, Daisuke 著作を一覧する
Fukuda, Ken-ichi 著作を一覧する
Kasai, Shinya 著作を一覧する
Hasegawa, Junko 著作を一覧する
Hayashida, Masakazu 著作を一覧する
Minami, Masabumi 著作を一覧する
Ikeda, Kazutaka 著作を一覧する
発行日: 2013年 8月 5日
出版者: Public library science
誌名: Plos one
巻: 8
号: 8
開始ページ: e70694
出版社 DOI: 10.1371/journal.pone.0070694
抄録: Individual differences in the sensitivity to fentanyl, a widely used opioid analgesic, lead to different proper doses of fentanyl, which can hamper effective pain treatment. Voltage-activated Ca2+ channels (VACCs) play a crucial role in the nervous system by controlling membrane excitability and calcium signaling. Ca(v)2.3 (R-type) VACCs have been especially thought to play critical roles in pain pathways and the analgesic effects of opioids. However, unknown is whether single-nucleotide polymorphisms (SNPs) of the human CACNA1E (calcium channel, voltage-dependent, R type, alpha 1E subunit) gene that encodes Ca(v)2.3 VACCs influence the analgesic effects of opioids. Thus, the present study examined associations between fentanyl sensitivity and SNPs in the human CACNA1E gene in 355 Japanese patients who underwent painful orofacial cosmetic surgery, including bone dissection. We first conducted linkage disequilibrium (LD) analyses of 223 SNPs in a region that contains the CACNA1E gene using genomic samples from 100 patients, and a total of 13 LD blocks with 42 Tag SNPs were observed within and around the CACNA1E gene region. In the preliminary study using the same 100 genomic samples, only the rs3845446 A/G SNP was significantly associated with perioperative fentanyl use among these 42 Tag SNPs. In a confirmatory study using the other 255 genomic samples, this SNP was also significantly associated with perioperative fentanyl use. Thus, we further analyzed associations between genotypes of this SNP and all of the clinical data using a total of 355 samples. The rs3845446 A/G SNP was associated with intraoperative fentanyl use, 24 h postoperative fentanyl requirements, and perioperative fentanyl use. Subjects who carried the minor G allele required significantly less fentanyl for pain control compared with subjects who did not carry this allele. Although further validation is needed, the present findings show the possibility of the involvement of CACNA1E gene polymorphisms in fentanyl sensitivity.
資料タイプ: article
URI: http://hdl.handle.net/2115/54121
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 井手 聡一郎

 

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