止吐5 -羟色胺受体拮抗剂昂丹司琼对CHRM3 rs2165870和TACR1 rs3755468单核苷酸多态性相关恶心的差异影响

IF 2.9 3区 医学 Q2 NEUROSCIENCES
Yuna Kang, Seii Ohka, Daisuke Nishizawa, Junko Hasegawa, Kyoko Nakayama, Kaori Yoshida, Kyotaro Koshika, Tatsuya Ichinohe, Kazutaka Ikeda
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引用次数: 0

摘要

术后恶心呕吐(PONV)是正颌手术后严重的并发症。据报道,胆碱能受体muscarinic 3 (CHRM3) rs2165870和速激肽受体1 (TACR1) rs3755468单核苷酸多态性(snp)与PONV有关。我们评估了这些snp对日本人群PONV的影响,这些人群在5-羟色胺(5-羟色胺)受体3A受体拮抗剂昂丹西酮预防PONV的情况下接受了正颌手术。121例患者插管后给予地塞米松,手术结束前给予昂丹司琼。采用11分数值评定量表(NRS)对PONV(麻醉终点后0-2小时或2-24小时[a.a.e])和是否给予甲氧氯普胺(0-2小时或2-24小时a.a.e)进行评分。如果患者主诉PONV且NRS评分≥4,则静脉给予甲氧氯普胺进行PONV抢救。对患者CHRM3 rs2165870和TACR1 rs3755468 snp进行基因分型,并统计分析这些snp与表型之间的相关性。在昂丹西酮影响减弱的情况下,CHRM3 rs2165870 AA型携带者接受甲氧氯普胺的比例显著高于GG和GA型携带者(P = 2.48 × 10- 2), NRS评分也显著高于GG和GA型携带者(P = 3.40 × 10- 2)。在昂丹西琼充分影响下,TACR1 rs3755468 CC携带者的NRS评分显著高于CT和TT携带者(P = 9.97 × 10- 3)。数值评定量表得分显示“时间”(昂丹司琼的作用)和“基因型”之间存在显著的交互作用(双向方差分析,P = 4.39 × 10- 2)。CHRM3 rs2165870基因AA型携带者与“时间”有显著相关性(P = 3.26 × 10- 2),而TACR1 rs3755468基因CC型携带者与“时间”无显著相关性(P < 0.05)。这些结果表明,昂丹司琼对与CHRM3相关的恶心有显著影响,而对与TACR1相关的恶心影响最小。这表明与CHRM3相关的恶心与与TACR1相关的恶心在质量上是不同的。昂丹司琼主要在血脑屏障外发挥作用,这可能导致与CHRM3和TACR1相关的恶心的不同影响。这些发现可能为未来针对依赖于CHRM3 rs2165870和TACR1 rs3755468 snp高危基因型的PONV量身定制预防措施提供方向。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Differential effects of antiemetic serotonin receptor antagonist Ondansetron on nausea associated with CHRM3 rs2165870 and TACR1 rs3755468 single-nucleotide polymorphisms.

Differential effects of antiemetic serotonin receptor antagonist Ondansetron on nausea associated with CHRM3 rs2165870 and TACR1 rs3755468 single-nucleotide polymorphisms.

Differential effects of antiemetic serotonin receptor antagonist Ondansetron on nausea associated with CHRM3 rs2165870 and TACR1 rs3755468 single-nucleotide polymorphisms.

Differential effects of antiemetic serotonin receptor antagonist Ondansetron on nausea associated with CHRM3 rs2165870 and TACR1 rs3755468 single-nucleotide polymorphisms.

Postoperative nausea and vomiting (PONV) after orthognathic surgery is a serious postoperative complication. The cholinergic receptor muscarinic 3 (CHRM3) rs2165870 and tachykinin receptor 1 (TACR1) rs3755468 single-nucleotide polymorphisms (SNPs) have been reported to be involved in PONV. We evaluated the impact of these SNPs on PONV in a Japanese population who underwent orthognathic surgery under PONV prophylaxis with the 5-hydroxytryptamine (serotonin) receptor 3A receptor antagonist ondansetron. In 121 patients, dexamethasone was administered after intubation, followed by ondansetron before the end of surgery. An 11-point numeric rating scale (NRS) score for PONV (0-2 h or 2-24 h after anesthesia endpoint [a.a.e.]) and the presence or absence of metoclopramide administration (0-2 h or 2-24 h a.a.e.) were evaluated. If patients complained of PONV and had an NRS score ≥ 4, then metoclopramide was administered intravenously for PONV rescue. Patients were genotyped for the CHRM3 rs2165870 and TACR1 rs3755468 SNPs, followed by the statistical analysis of associations between these SNPs and phenotypes. AA carriers of CHRM3 rs2165870 received metoclopramide at a significantly higher rate (P = 2.48 × 10- 2) and had higher NRS scores (P = 3.40 × 10- 2) under a diminished influence of ondansetron than GG and GA carriers. CC carriers of TACR1 rs3755468 had significantly higher NRS scores under the sufficient influence of ondansetron than CT and TT carriers (P = 9.97 × 10- 3). Numeric rating scale scores showed a significant interaction between "time" (the effect of ondansetron) and "genotype" (two-way analysis of variance, P = 4.39 × 10- 2). AA carriers of CHRM3 rs2165870 were significantly associated with "time" (P = 3.26 × 10- 2), and CC carriers of TACR1 rs3755468 were not (P > 0.05). These results suggest that ondansetron significantly affects nausea that is associated with CHRM3, whereas it has a minimal effect on nausea that is associated with TACR1. This indicates that nausea that is associated with CHRM3 is qualitatively different from nausea that is associated with TACR1. Ondansetron mainly exerts its effects outside the blood-brain barrier, which may lead to differential impacts on nausea that is associated with CHRM3 and TACR1. These findings may provide future directions for tailor-made preventive measures against PONV that depend on high-risk genotypes of the CHRM3 rs2165870 and TACR1 rs3755468 SNPs.

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来源期刊
Molecular Brain
Molecular Brain NEUROSCIENCES-
CiteScore
7.30
自引率
0.00%
发文量
97
审稿时长
>12 weeks
期刊介绍: Molecular Brain is an open access, peer-reviewed journal that considers manuscripts on all aspects of studies on the nervous system at the molecular, cellular, and systems level providing a forum for scientists to communicate their findings. Molecular brain research is a rapidly expanding research field in which integrative approaches at the genetic, molecular, cellular and synaptic levels yield key information about the physiological and pathological brain. These studies involve the use of a wide range of modern techniques in molecular biology, genomics, proteomics, imaging and electrophysiology.
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