Association between genetic polymorphisms in Ca(v)2.3 (R-type) Ca2+ channels and fentanyl sensitivity in patients undergoing painful cosmetic surgery.
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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DOI：
10.1371/journal.pone.0070694
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Ikeda K
中科院分区：
文献类型：
--
作者：
Ide S;Nishizawa D;Fukuda K;Kasai S;Hasegawa J;Hayashida M;Minami M;Ikeda K
对芬太尼（一种广泛使用的阿片类镇痛药）敏感性的个体差异导致芬太尼的适当剂量不同，这可能会妨碍有效的疼痛治疗。电压激活的钙离子通道（VACCs）通过控制膜兴奋性和钙信号在神经系统中起着至关重要的作用。Cav2.3（R型）VACCs特别被认为在疼痛通路和阿片类药物的镇痛作用中发挥关键作用。然而，目前尚不清楚编码Cav2.3 VACC的人类CACNA 1 E（钙通道，电压依赖性，R型，α 1 E亚基）基因的单核苷酸多态性（SNP）是否会影响阿片类药物的镇痛作用。因此，本研究在355名接受痛苦的口面部美容手术（包括骨切除）的日本患者中检查了芬太尼敏感性与人类CACNA 1 E基因中SNP之间的关联。我们首先使用来自100名患者的基因组样本对包含CACNA 1 E基因的区域中的223个SNP进行了连锁不平衡（LD）分析，在CACNA 1 E基因区域内和周围观察到总共13个LD区块，其中42个标签SNP。在使用相同的100个基因组样本的初步研究中，在这42个标签SNP中，只有rs3845446 A/G SNP与围手术期芬太尼使用显著相关。在使用其他255个基因组样本的验证性研究中，该SNP也与围手术期芬太尼使用显著相关。因此，我们使用总共355个样本进一步分析了该SNP的基因型与所有临床数据之间的关联。rs3845446 A/G SNP与术中芬太尼使用、术后24 h芬太尼需求和围手术期芬太尼使用相关。与不携带该等位基因的受试者相比，携带次要G等位基因的受试者需要显著较少的芬太尼用于疼痛控制。虽然需要进一步验证，目前的研究结果表明，CACNA 1 E基因多态性参与芬太尼敏感性的可能性。
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. Cav2.3 (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 Cav2.3 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.
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影响因子：
30.8
作者：
de Bakker, PIW;Yelensky, R;Altshuler, D
通讯作者：
Altshuler, D
影响因子：
8.2
作者：
Holmkvist, J.;Tojjar, D.;Groop, L.
通讯作者：
Groop, L.
影响因子：
7.4
作者：
Bisgaard, T;Klarskov, B;Kehlet, H
通讯作者：
Kehlet, H
DOI：
10.1016/s0169-328x(97)00353-7
发表时间：
1998-03-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Loh, HH;Liu, HC;Wei, LN
通讯作者：
Wei, LN
影响因子：
56.9
作者：
Gabriel, SB;Schaffner, SF;Altshuler, D
通讯作者：
Altshuler, D