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Genetic Polymorphisms and In Silico Mutagenesis Analyses of CYP2C9, CYP2D6, and CYPOR Genes in the Pakistani Population
Diverse distributions of pharmacogenetically relevant variants of highly polymorphic CYP2C9, CYP2D6 and CYPOR genes are responsible for some varied drug responses observed across human populations. There is limited data available regarding the pharmacogenetic polymorphisms and frequency distribution...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211126/ https://www.ncbi.nlm.nih.gov/pubmed/30360443 http://dx.doi.org/10.3390/genes9100514 |
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author | Ahmed, Shabbir Zhou, Jie Zhou, Zhan Chen, Shu-Qing |
author_facet | Ahmed, Shabbir Zhou, Jie Zhou, Zhan Chen, Shu-Qing |
author_sort | Ahmed, Shabbir |
collection | PubMed |
description | Diverse distributions of pharmacogenetically relevant variants of highly polymorphic CYP2C9, CYP2D6 and CYPOR genes are responsible for some varied drug responses observed across human populations. There is limited data available regarding the pharmacogenetic polymorphisms and frequency distributions of major allele variants in the Pakistani population. The present in silico mutagenesis study conducted on genotype pharmacogenetic variants and comparative analysis with a global population aims to extend the currently limited pharmacogenetic available evidence for the indigenous Pakistani population. Extracted genomic DNA from 244 healthy individuals’ venous blood samples were amplified for distinct variant loci in the CYP2C9, CYP2D6 and CYPOR genes. Two-way sequencing results were compared with standard PubMed data and sequence variant loci confirmed by Chromas. This study revealed significant variations in CYP2C9 (rs1799853, rs1057910 and rs72558189), CYP2D6 (rs16947 and rs1135840), and CYPOR (rs1057868, rs781919285 and rs562750402) variants in intraethnic and interethnic frequency distributions. In silico mutagenesis and three-dimensional protein structural alignment analysis approaches clearly exposed the possible varied impact of rare CYPOR (rs781919285 and rs562750402) single nucleotide polymorphisms (SNPs) and confirmed that the influences of CYP2C9 and CYP2D6 variants are consistent with what was found in earlier studies. This investigation highlighted the need to study pharmacogenetic relevance loci and documentation since evidence could be utilized to elucidate genetic backgrounds of drug metabolism, and provide a basis for future pharmacogenomic studies and adequate dose adjustments in Pakistani and global populations. |
format | Online Article Text |
id | pubmed-6211126 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62111262018-11-02 Genetic Polymorphisms and In Silico Mutagenesis Analyses of CYP2C9, CYP2D6, and CYPOR Genes in the Pakistani Population Ahmed, Shabbir Zhou, Jie Zhou, Zhan Chen, Shu-Qing Genes (Basel) Article Diverse distributions of pharmacogenetically relevant variants of highly polymorphic CYP2C9, CYP2D6 and CYPOR genes are responsible for some varied drug responses observed across human populations. There is limited data available regarding the pharmacogenetic polymorphisms and frequency distributions of major allele variants in the Pakistani population. The present in silico mutagenesis study conducted on genotype pharmacogenetic variants and comparative analysis with a global population aims to extend the currently limited pharmacogenetic available evidence for the indigenous Pakistani population. Extracted genomic DNA from 244 healthy individuals’ venous blood samples were amplified for distinct variant loci in the CYP2C9, CYP2D6 and CYPOR genes. Two-way sequencing results were compared with standard PubMed data and sequence variant loci confirmed by Chromas. This study revealed significant variations in CYP2C9 (rs1799853, rs1057910 and rs72558189), CYP2D6 (rs16947 and rs1135840), and CYPOR (rs1057868, rs781919285 and rs562750402) variants in intraethnic and interethnic frequency distributions. In silico mutagenesis and three-dimensional protein structural alignment analysis approaches clearly exposed the possible varied impact of rare CYPOR (rs781919285 and rs562750402) single nucleotide polymorphisms (SNPs) and confirmed that the influences of CYP2C9 and CYP2D6 variants are consistent with what was found in earlier studies. This investigation highlighted the need to study pharmacogenetic relevance loci and documentation since evidence could be utilized to elucidate genetic backgrounds of drug metabolism, and provide a basis for future pharmacogenomic studies and adequate dose adjustments in Pakistani and global populations. MDPI 2018-10-22 /pmc/articles/PMC6211126/ /pubmed/30360443 http://dx.doi.org/10.3390/genes9100514 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ahmed, Shabbir Zhou, Jie Zhou, Zhan Chen, Shu-Qing Genetic Polymorphisms and In Silico Mutagenesis Analyses of CYP2C9, CYP2D6, and CYPOR Genes in the Pakistani Population |
title | Genetic Polymorphisms and In Silico Mutagenesis Analyses of CYP2C9, CYP2D6, and CYPOR Genes in the Pakistani Population |
title_full | Genetic Polymorphisms and In Silico Mutagenesis Analyses of CYP2C9, CYP2D6, and CYPOR Genes in the Pakistani Population |
title_fullStr | Genetic Polymorphisms and In Silico Mutagenesis Analyses of CYP2C9, CYP2D6, and CYPOR Genes in the Pakistani Population |
title_full_unstemmed | Genetic Polymorphisms and In Silico Mutagenesis Analyses of CYP2C9, CYP2D6, and CYPOR Genes in the Pakistani Population |
title_short | Genetic Polymorphisms and In Silico Mutagenesis Analyses of CYP2C9, CYP2D6, and CYPOR Genes in the Pakistani Population |
title_sort | genetic polymorphisms and in silico mutagenesis analyses of cyp2c9, cyp2d6, and cypor genes in the pakistani population |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211126/ https://www.ncbi.nlm.nih.gov/pubmed/30360443 http://dx.doi.org/10.3390/genes9100514 |
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