Genetic landscape of 125 pharmacogenes in Chinese from the Chinese Millionome Database

Abstract Inter-individual differences of drug responses could be attributed to genetic variants of pharmacogenes such as cytochrome P450 (CYP), phase 2 enzymes, and transporters. In contrast to extensive studies on the genetic polymorphisms of CYP gene, genetic mutation spectrum of other pharmacogen...

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Autores principales:	Guangzhao Qi, Jingmin Zhang, Chao Han, Yubing Zhou, Duolu Li, Pengfei Ma
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8aaecce1c52a46daa08aede5d1ff68f8
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spelling	oai:doaj.org-article:8aaecce1c52a46daa08aede5d1ff68f82021-12-02T18:51:36ZGenetic landscape of 125 pharmacogenes in Chinese from the Chinese Millionome Database10.1038/s41598-021-98877-x2045-2322https://doaj.org/article/8aaecce1c52a46daa08aede5d1ff68f82021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98877-xhttps://doaj.org/toc/2045-2322Abstract Inter-individual differences of drug responses could be attributed to genetic variants of pharmacogenes such as cytochrome P450 (CYP), phase 2 enzymes, and transporters. In contrast to extensive studies on the genetic polymorphisms of CYP gene, genetic mutation spectrum of other pharmacogenes was under-representative in the pharmacogenetics investigations. Here we studied the genetic variations of 125 pharmacogenes including drug transporters, non-CYP phase 1 enzymes, phase 2 enzymes, nuclear receptors and others in Chinese from the Chinese Millionome Database (CMDB), of which 38,188 variants were identified. Computational analyses of the 2554 exonic variants found 617 deleterious missense variants, 91.1% of which were rare, and of the 54 loss-of-function (splice acceptor, splice donor, start lost, and stop gained) variants, 53 (98.1%) were rare. These results suggested an enrichment of rare variants in functional ones for pharmacogenes. Certain common functional variants including NUDT15 13:48611934 G/A (rs186364861), UGT1A1 2:234676872 C/T (rs34946978), and ALDH2 12:112241766 G/A (rs671) were population-specific for CMDB Chinese because they were absent (with a zero of variant allele frequency) or very rare in other gnomAD populations. These findings might be useful for the further pharmacogenomics research and clinical application in Chinese.Guangzhao QiJingmin ZhangChao HanYubing ZhouDuolu LiPengfei MaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Guangzhao Qi Jingmin Zhang Chao Han Yubing Zhou Duolu Li Pengfei Ma Genetic landscape of 125 pharmacogenes in Chinese from the Chinese Millionome Database
description	Abstract Inter-individual differences of drug responses could be attributed to genetic variants of pharmacogenes such as cytochrome P450 (CYP), phase 2 enzymes, and transporters. In contrast to extensive studies on the genetic polymorphisms of CYP gene, genetic mutation spectrum of other pharmacogenes was under-representative in the pharmacogenetics investigations. Here we studied the genetic variations of 125 pharmacogenes including drug transporters, non-CYP phase 1 enzymes, phase 2 enzymes, nuclear receptors and others in Chinese from the Chinese Millionome Database (CMDB), of which 38,188 variants were identified. Computational analyses of the 2554 exonic variants found 617 deleterious missense variants, 91.1% of which were rare, and of the 54 loss-of-function (splice acceptor, splice donor, start lost, and stop gained) variants, 53 (98.1%) were rare. These results suggested an enrichment of rare variants in functional ones for pharmacogenes. Certain common functional variants including NUDT15 13:48611934 G/A (rs186364861), UGT1A1 2:234676872 C/T (rs34946978), and ALDH2 12:112241766 G/A (rs671) were population-specific for CMDB Chinese because they were absent (with a zero of variant allele frequency) or very rare in other gnomAD populations. These findings might be useful for the further pharmacogenomics research and clinical application in Chinese.
format	article
author	Guangzhao Qi Jingmin Zhang Chao Han Yubing Zhou Duolu Li Pengfei Ma
author_facet	Guangzhao Qi Jingmin Zhang Chao Han Yubing Zhou Duolu Li Pengfei Ma
author_sort	Guangzhao Qi
title	Genetic landscape of 125 pharmacogenes in Chinese from the Chinese Millionome Database
title_short	Genetic landscape of 125 pharmacogenes in Chinese from the Chinese Millionome Database
title_full	Genetic landscape of 125 pharmacogenes in Chinese from the Chinese Millionome Database
title_fullStr	Genetic landscape of 125 pharmacogenes in Chinese from the Chinese Millionome Database
title_full_unstemmed	Genetic landscape of 125 pharmacogenes in Chinese from the Chinese Millionome Database
title_sort	genetic landscape of 125 pharmacogenes in chinese from the chinese millionome database
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8aaecce1c52a46daa08aede5d1ff68f8
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Genetic landscape of 125 pharmacogenes in Chinese from the Chinese Millionome Database

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