Cargando…

Detection of CYP2C19 Genetic Variants in Malaysian Orang Asli from Massively Parallel Sequencing Data

The human cytochrome P450 (CYP) is a superfamily of enzymes that have been a focus in research for decades due to their prominent role in drug metabolism. CYP2C is one of the major subfamilies which metabolize more than 10% of all clinically used drugs. In the context of CYP2C19, several key genetic...

Descripción completa

Detalles Bibliográficos
Autores principales: Ang, Geik Yong, Yu, Choo Yee, Subramaniam, Vinothini, Abdul Khalid, Mohd Ikhmal Hanif, Tuan Abdu Aziz, Tuan Azlin, Johari James, Richard, Ahmad, Aminuddin, Abdul Rahman, Thuhairah, Mohd Nor, Fadzilah, Ismail, Adzrool Idzwan, Md. Isa, Kamarudzaman, Salleh, Hood, Teh, Lay Kek, Salleh, Mohd Zaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087908/
https://www.ncbi.nlm.nih.gov/pubmed/27798644
http://dx.doi.org/10.1371/journal.pone.0164169
_version_ 1782463994205831168
author Ang, Geik Yong
Yu, Choo Yee
Subramaniam, Vinothini
Abdul Khalid, Mohd Ikhmal Hanif
Tuan Abdu Aziz, Tuan Azlin
Johari James, Richard
Ahmad, Aminuddin
Abdul Rahman, Thuhairah
Mohd Nor, Fadzilah
Ismail, Adzrool Idzwan
Md. Isa, Kamarudzaman
Salleh, Hood
Teh, Lay Kek
Salleh, Mohd Zaki
author_facet Ang, Geik Yong
Yu, Choo Yee
Subramaniam, Vinothini
Abdul Khalid, Mohd Ikhmal Hanif
Tuan Abdu Aziz, Tuan Azlin
Johari James, Richard
Ahmad, Aminuddin
Abdul Rahman, Thuhairah
Mohd Nor, Fadzilah
Ismail, Adzrool Idzwan
Md. Isa, Kamarudzaman
Salleh, Hood
Teh, Lay Kek
Salleh, Mohd Zaki
author_sort Ang, Geik Yong
collection PubMed
description The human cytochrome P450 (CYP) is a superfamily of enzymes that have been a focus in research for decades due to their prominent role in drug metabolism. CYP2C is one of the major subfamilies which metabolize more than 10% of all clinically used drugs. In the context of CYP2C19, several key genetic variations that alter the enzyme’s activity have been identified and catalogued in the CYP allele nomenclature database. In this study, we investigated the presence of well-established variants as well as novel polymorphisms in the CYP2C19 gene of 62 Orang Asli from the Peninsular Malaysia. A total of 449 genetic variants were detected including 70 novel polymorphisms; 417 SNPs were located in introns, 23 in upstream, 7 in exons, and 2 in downstream regions. Five alleles and seven genotypes were inferred based on the polymorphisms that were found. Null alleles that were observed include CYP2C19*3 (6.5%), *2 (5.7%) and *35 (2.4%) whereas allele with increased function *17 was detected at a frequency of 4.8%. The normal metabolizer genotype was the most predominant (66.1%), followed by intermediate metabolizer (19.4%), rapid metabolizer (9.7%) and poor metabolizer (4.8%) genotypes. Findings from this study provide further insights into the CYP2C19 genetic profile of the Orang Asli as previously unreported variant alleles were detected through the use of massively parallel sequencing technology platform. The systematic and comprehensive analysis of CYP2C19 will allow uncharacterized variants that are present in the Orang Asli to be included in the genotyping panel in the future.
format Online
Article
Text
id pubmed-5087908
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-50879082016-11-15 Detection of CYP2C19 Genetic Variants in Malaysian Orang Asli from Massively Parallel Sequencing Data Ang, Geik Yong Yu, Choo Yee Subramaniam, Vinothini Abdul Khalid, Mohd Ikhmal Hanif Tuan Abdu Aziz, Tuan Azlin Johari James, Richard Ahmad, Aminuddin Abdul Rahman, Thuhairah Mohd Nor, Fadzilah Ismail, Adzrool Idzwan Md. Isa, Kamarudzaman Salleh, Hood Teh, Lay Kek Salleh, Mohd Zaki PLoS One Research Article The human cytochrome P450 (CYP) is a superfamily of enzymes that have been a focus in research for decades due to their prominent role in drug metabolism. CYP2C is one of the major subfamilies which metabolize more than 10% of all clinically used drugs. In the context of CYP2C19, several key genetic variations that alter the enzyme’s activity have been identified and catalogued in the CYP allele nomenclature database. In this study, we investigated the presence of well-established variants as well as novel polymorphisms in the CYP2C19 gene of 62 Orang Asli from the Peninsular Malaysia. A total of 449 genetic variants were detected including 70 novel polymorphisms; 417 SNPs were located in introns, 23 in upstream, 7 in exons, and 2 in downstream regions. Five alleles and seven genotypes were inferred based on the polymorphisms that were found. Null alleles that were observed include CYP2C19*3 (6.5%), *2 (5.7%) and *35 (2.4%) whereas allele with increased function *17 was detected at a frequency of 4.8%. The normal metabolizer genotype was the most predominant (66.1%), followed by intermediate metabolizer (19.4%), rapid metabolizer (9.7%) and poor metabolizer (4.8%) genotypes. Findings from this study provide further insights into the CYP2C19 genetic profile of the Orang Asli as previously unreported variant alleles were detected through the use of massively parallel sequencing technology platform. The systematic and comprehensive analysis of CYP2C19 will allow uncharacterized variants that are present in the Orang Asli to be included in the genotyping panel in the future. Public Library of Science 2016-10-31 /pmc/articles/PMC5087908/ /pubmed/27798644 http://dx.doi.org/10.1371/journal.pone.0164169 Text en © 2016 Ang et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Ang, Geik Yong
Yu, Choo Yee
Subramaniam, Vinothini
Abdul Khalid, Mohd Ikhmal Hanif
Tuan Abdu Aziz, Tuan Azlin
Johari James, Richard
Ahmad, Aminuddin
Abdul Rahman, Thuhairah
Mohd Nor, Fadzilah
Ismail, Adzrool Idzwan
Md. Isa, Kamarudzaman
Salleh, Hood
Teh, Lay Kek
Salleh, Mohd Zaki
Detection of CYP2C19 Genetic Variants in Malaysian Orang Asli from Massively Parallel Sequencing Data
title Detection of CYP2C19 Genetic Variants in Malaysian Orang Asli from Massively Parallel Sequencing Data
title_full Detection of CYP2C19 Genetic Variants in Malaysian Orang Asli from Massively Parallel Sequencing Data
title_fullStr Detection of CYP2C19 Genetic Variants in Malaysian Orang Asli from Massively Parallel Sequencing Data
title_full_unstemmed Detection of CYP2C19 Genetic Variants in Malaysian Orang Asli from Massively Parallel Sequencing Data
title_short Detection of CYP2C19 Genetic Variants in Malaysian Orang Asli from Massively Parallel Sequencing Data
title_sort detection of cyp2c19 genetic variants in malaysian orang asli from massively parallel sequencing data
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087908/
https://www.ncbi.nlm.nih.gov/pubmed/27798644
http://dx.doi.org/10.1371/journal.pone.0164169
work_keys_str_mv AT anggeikyong detectionofcyp2c19geneticvariantsinmalaysianorangaslifrommassivelyparallelsequencingdata
AT yuchooyee detectionofcyp2c19geneticvariantsinmalaysianorangaslifrommassivelyparallelsequencingdata
AT subramaniamvinothini detectionofcyp2c19geneticvariantsinmalaysianorangaslifrommassivelyparallelsequencingdata
AT abdulkhalidmohdikhmalhanif detectionofcyp2c19geneticvariantsinmalaysianorangaslifrommassivelyparallelsequencingdata
AT tuanabduaziztuanazlin detectionofcyp2c19geneticvariantsinmalaysianorangaslifrommassivelyparallelsequencingdata
AT joharijamesrichard detectionofcyp2c19geneticvariantsinmalaysianorangaslifrommassivelyparallelsequencingdata
AT ahmadaminuddin detectionofcyp2c19geneticvariantsinmalaysianorangaslifrommassivelyparallelsequencingdata
AT abdulrahmanthuhairah detectionofcyp2c19geneticvariantsinmalaysianorangaslifrommassivelyparallelsequencingdata
AT mohdnorfadzilah detectionofcyp2c19geneticvariantsinmalaysianorangaslifrommassivelyparallelsequencingdata
AT ismailadzroolidzwan detectionofcyp2c19geneticvariantsinmalaysianorangaslifrommassivelyparallelsequencingdata
AT mdisakamarudzaman detectionofcyp2c19geneticvariantsinmalaysianorangaslifrommassivelyparallelsequencingdata
AT sallehhood detectionofcyp2c19geneticvariantsinmalaysianorangaslifrommassivelyparallelsequencingdata
AT tehlaykek detectionofcyp2c19geneticvariantsinmalaysianorangaslifrommassivelyparallelsequencingdata
AT sallehmohdzaki detectionofcyp2c19geneticvariantsinmalaysianorangaslifrommassivelyparallelsequencingdata