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长程 PCR 基础的下一代测序在一般麻醉患者中丙泊酚药代动力学和药效学研究中的应用。

Longrange PCR-based next-generation sequencing in pharmacokinetics and pharmacodynamics study of propofol among patients under general anaesthesia.

机构信息

Institute of Human Genetics, Polish Academy of Sciences, Strzeszynska 32, 60-479, Poznan, Poland.

The NanoBioMedical Centre, Adam Mickiewicz University, Umultowska 85, 61-614, Poznan, Poland.

出版信息

Sci Rep. 2017 Nov 13;7(1):15399. doi: 10.1038/s41598-017-15657-2.

DOI:10.1038/s41598-017-15657-2
PMID:29133890
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5684313/
Abstract

The individual response of patients to propofol results from the influence of genetic factors. However, the state of knowledge in this matter still remains insufficient. The aim of our study was to determine genetic predictors of variable pharmacokinetics and pharmacodynamics of propofol within selected 9 genes coding for propofol biotransformation enzymes, receptors and transporters. Our studies are the first extensive pharmaocgenetics research of propofol using high throughput sequencing technology. After the design and optimization of long range PCR-based next-generation sequencing experiment, we screened promoter and coding sequences of all genes analyzed among 87 Polish patients undergoing general anaesthesia with propofol. Initially we found that two variants, c.516 G > T in the CYP2B6 gene and c.2677 T > G in the ABCB1 gene, significantly correlate with propofol's metabolic profile, however after Bonferroni correction the P-values were not statistically significant. Our results suggest, that variants within the CYP2B6 and ABCB1 genes correlate stronger with propofol's metabolic profile compared to other 7 genes. CYP2B6 and ABCB1 variants can play a potentially important role in response to this anaesthetic and they are promising object for further studies.

摘要

患者对丙泊酚的个体反应是由遗传因素影响的。然而,在这方面的知识状况仍然不足。我们的研究目的是确定 9 个编码丙泊酚生物转化酶、受体和转运体的基因中,与丙泊酚药代动力学和药效动力学变异性相关的遗传预测因子。我们的研究是使用高通量测序技术对丙泊酚进行的首次广泛的药物遗传学研究。在设计和优化基于长距离 PCR 的下一代测序实验后,我们在 87 名接受丙泊酚全身麻醉的波兰患者中筛选了所有分析基因的启动子和编码序列。最初我们发现,CYP2B6 基因中的 c.516G>T 和 ABCB1 基因中的 c.2677T>G 两个变体与丙泊酚的代谢谱显著相关,但经 Bonferroni 校正后 P 值无统计学意义。我们的结果表明,CYP2B6 和 ABCB1 基因内的变体与丙泊酚的代谢谱相关性比其他 7 个基因更强。CYP2B6 和 ABCB1 变体可能在对这种麻醉剂的反应中发挥重要作用,它们是进一步研究的有前途的对象。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b14e/5684313/10915c4f1b42/41598_2017_15657_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b14e/5684313/fd6d9ea41055/41598_2017_15657_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b14e/5684313/6174e57de649/41598_2017_15657_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b14e/5684313/10915c4f1b42/41598_2017_15657_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b14e/5684313/fd6d9ea41055/41598_2017_15657_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b14e/5684313/6174e57de649/41598_2017_15657_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b14e/5684313/10915c4f1b42/41598_2017_15657_Fig3_HTML.jpg

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本文引用的文献

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2
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Eur J Drug Metab Pharmacokinet. 2016 Oct;41(5):511-5. doi: 10.1007/s13318-015-0289-y.
3
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NGS study of glucocorticoid response genes in inflammatory bowel disease patients.炎症性肠病患者糖皮质激素反应基因的二代测序研究
Arch Med Sci. 2019 May 5;17(2):417-433. doi: 10.5114/aoms.2019.84470. eCollection 2021.
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