Association of Polymorphisms in Pharmacogenetic Candidate Genes with Propofol Susceptibility

Abstract Significant individual susceptibility to intravenous anesthetic propofol exists. The etiology of individual variability in the response to propofol may be influenced by genetic polymorphisms in metabolic and functional pathways. With current pharmacogenetics and modern molecular biology tec...

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Autores principales:	Qi Zhong, Xiangdong Chen, Yan Zhao, Ru Liu, Shanglong Yao
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4d074c98dc3c4f4386470cadba238ca8
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spelling	oai:doaj.org-article:4d074c98dc3c4f4386470cadba238ca82021-12-02T12:30:33ZAssociation of Polymorphisms in Pharmacogenetic Candidate Genes with Propofol Susceptibility10.1038/s41598-017-03229-32045-2322https://doaj.org/article/4d074c98dc3c4f4386470cadba238ca82017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03229-3https://doaj.org/toc/2045-2322Abstract Significant individual susceptibility to intravenous anesthetic propofol exists. The etiology of individual variability in the response to propofol may be influenced by genetic polymorphisms in metabolic and functional pathways. With current pharmacogenetics and modern molecular biology technologies, it is possible to study the influence of genetic polymorphisms on susceptibility to propofol. When inducing general anesthesia with intravenous propofol, high individual susceptibility to propofol was found. Using Sequenom MassARRAY single-nucleotide polymorphism (SNP) genotyping, we identified a mutation (rs6313) in the 5HT2A gene that was correlated to individual susceptibility to propofol effect-site concentration (Cep) and onset time of propofol induction. Carriers of the minor allele (G) of 5HT2A rs6313 required less propofol (20% decrease in Cep) and less time (40% decrease in onset time) to induce anesthesia. Moreover, associations were found between the gamma-aminobutyric acid (GABA) receptor SNP rs2279020 and the SCN9A SNP rs6746030 and the susceptibility of bispectral index (BIS) after propofol-induced anesthesia. In addition, dominant mutations in GABAA1 rs2279020, GABAA2 rs11503014, and CHRM2 rs1824024 were putatively associated with cardiovascular susceptibility to propofol anesthesia. No gene-gene interactions were found through a standardized measure of linkage disequilibrium and a multifactor dimensionality reduction analysis. Our results suggest that genetic polymorphisms related to mechanisms of propofol anesthesia are involved in propofol susceptibility.Qi ZhongXiangdong ChenYan ZhaoRu LiuShanglong YaoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Qi Zhong Xiangdong Chen Yan Zhao Ru Liu Shanglong Yao Association of Polymorphisms in Pharmacogenetic Candidate Genes with Propofol Susceptibility
description	Abstract Significant individual susceptibility to intravenous anesthetic propofol exists. The etiology of individual variability in the response to propofol may be influenced by genetic polymorphisms in metabolic and functional pathways. With current pharmacogenetics and modern molecular biology technologies, it is possible to study the influence of genetic polymorphisms on susceptibility to propofol. When inducing general anesthesia with intravenous propofol, high individual susceptibility to propofol was found. Using Sequenom MassARRAY single-nucleotide polymorphism (SNP) genotyping, we identified a mutation (rs6313) in the 5HT2A gene that was correlated to individual susceptibility to propofol effect-site concentration (Cep) and onset time of propofol induction. Carriers of the minor allele (G) of 5HT2A rs6313 required less propofol (20% decrease in Cep) and less time (40% decrease in onset time) to induce anesthesia. Moreover, associations were found between the gamma-aminobutyric acid (GABA) receptor SNP rs2279020 and the SCN9A SNP rs6746030 and the susceptibility of bispectral index (BIS) after propofol-induced anesthesia. In addition, dominant mutations in GABAA1 rs2279020, GABAA2 rs11503014, and CHRM2 rs1824024 were putatively associated with cardiovascular susceptibility to propofol anesthesia. No gene-gene interactions were found through a standardized measure of linkage disequilibrium and a multifactor dimensionality reduction analysis. Our results suggest that genetic polymorphisms related to mechanisms of propofol anesthesia are involved in propofol susceptibility.
format	article
author	Qi Zhong Xiangdong Chen Yan Zhao Ru Liu Shanglong Yao
author_facet	Qi Zhong Xiangdong Chen Yan Zhao Ru Liu Shanglong Yao
author_sort	Qi Zhong
title	Association of Polymorphisms in Pharmacogenetic Candidate Genes with Propofol Susceptibility
title_short	Association of Polymorphisms in Pharmacogenetic Candidate Genes with Propofol Susceptibility
title_full	Association of Polymorphisms in Pharmacogenetic Candidate Genes with Propofol Susceptibility
title_fullStr	Association of Polymorphisms in Pharmacogenetic Candidate Genes with Propofol Susceptibility
title_full_unstemmed	Association of Polymorphisms in Pharmacogenetic Candidate Genes with Propofol Susceptibility
title_sort	association of polymorphisms in pharmacogenetic candidate genes with propofol susceptibility
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/4d074c98dc3c4f4386470cadba238ca8
work_keys_str_mv	AT qizhong associationofpolymorphismsinpharmacogeneticcandidategeneswithpropofolsusceptibility AT xiangdongchen associationofpolymorphismsinpharmacogeneticcandidategeneswithpropofolsusceptibility AT yanzhao associationofpolymorphismsinpharmacogeneticcandidategeneswithpropofolsusceptibility AT ruliu associationofpolymorphismsinpharmacogeneticcandidategeneswithpropofolsusceptibility AT shanglongyao associationofpolymorphismsinpharmacogeneticcandidategeneswithpropofolsusceptibility
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Association of Polymorphisms in Pharmacogenetic Candidate Genes with Propofol Susceptibility

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