Genetic diversity of ‘Very Important Pharmacogenes’ in two South-Asian populations

Objectives Reliable identification of population-specific variants is important for building the single nucleotide polymorphism (SNP) profile. In this study, genomic variation using allele frequency differences of pharmacologically important genes for Gujarati Indians in Houston (GIH) and Indian Tel...

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Autores principales:	Neeraj Bharti, Ruma Banerjee, Archana Achalere, Sunitha Manjari Kasibhatla, Rajendra Joshi
Formato:	article
Lenguaje:	EN
Publicado:	PeerJ Inc. 2021
Materias:	GIH ITU 1000 Genomes Project gnomAD SNPs Allele frequency Medicine R
Acceso en línea:	https://doaj.org/article/f830bd248e5d4731844d7a9f9557d854
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spelling	oai:doaj.org-article:f830bd248e5d4731844d7a9f9557d8542021-11-12T15:05:06ZGenetic diversity of ‘Very Important Pharmacogenes’ in two South-Asian populations10.7717/peerj.122942167-8359https://doaj.org/article/f830bd248e5d4731844d7a9f9557d8542021-11-01T00:00:00Zhttps://peerj.com/articles/12294.pdfhttps://peerj.com/articles/12294/https://doaj.org/toc/2167-8359Objectives Reliable identification of population-specific variants is important for building the single nucleotide polymorphism (SNP) profile. In this study, genomic variation using allele frequency differences of pharmacologically important genes for Gujarati Indians in Houston (GIH) and Indian Telugu in the U.K. (ITU) from the 1000 Genomes Project vis-à-vis global population data was studied to understand its role in drug response. Methods Joint genotyping approach was used to derive variants of GIH and ITU independently. SNPs of both these populations with significant allele frequency variation (minor allele frequency ≥ 0.05) with super-populations from the 1000 Genomes Project and gnomAD based on Chi-square distribution with p-value of ≤ 0.05 and Bonferroni’s multiple adjustment tests were identified. Population stratification and fixation index analysis was carried out to understand genetic differentiation. Functional annotation of variants was carried out using SnpEff, VEP and CADD score. Results Population stratification of VIP genes revealed four clusters viz., single cluster of GIH and ITU, one cluster each of East Asian, European, African populations and Admixed American was found to be admixed. A total of 13 SNPs belonging to ten pharmacogenes were identified to have significant allele frequency variation in both GIH and ITU populations as compared to one or more super-populations. These SNPs belong to VKORC1 (rs17708472, rs2359612, rs8050894) involved in Vitamin K cycle, cytochrome P450 isoforms CYP2C9 (rs1057910), CYP2B6 (rs3211371), CYP2A2 (rs4646425) and CYP2A4 (rs4646440); ATP-binding cassette (ABC) transporter ABCB1 (rs12720067), DPYD1 (rs12119882, rs56160474) involved in pyrimidine metabolism, methyltransferase COMT (rs9332377) and transcriptional factor NR1I2 (rs6785049). SNPs rs1544410 (VDR), rs2725264 (ABCG2), rs5215 and rs5219 (KCNJ11) share high fixation index (≥ 0.5) with either EAS/AFR populations. Missense variants rs1057910 (CYP2C9), rs1801028 (DRD2) and rs1138272 (GSTP1), rs116855232 (NUDT15); intronic variants rs1131341 (NQO1) and rs115349832 (DPYD) are identified to be ‘deleterious’. Conclusions Analysis of SNPs pertaining to pharmacogenes in GIH and ITU populations using population structure, fixation index and allele frequency variation provides a premise for understanding the role of genetic diversity in drug response in Asian Indians.Neeraj BhartiRuma BanerjeeArchana AchalereSunitha Manjari KasibhatlaRajendra JoshiPeerJ Inc.articleGIHITU1000 Genomes ProjectgnomADSNPsAllele frequencyMedicineRENPeerJ, Vol 9, p e12294 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	GIH ITU 1000 Genomes Project gnomAD SNPs Allele frequency Medicine R
spellingShingle	GIH ITU 1000 Genomes Project gnomAD SNPs Allele frequency Medicine R Neeraj Bharti Ruma Banerjee Archana Achalere Sunitha Manjari Kasibhatla Rajendra Joshi Genetic diversity of ‘Very Important Pharmacogenes’ in two South-Asian populations
description	Objectives Reliable identification of population-specific variants is important for building the single nucleotide polymorphism (SNP) profile. In this study, genomic variation using allele frequency differences of pharmacologically important genes for Gujarati Indians in Houston (GIH) and Indian Telugu in the U.K. (ITU) from the 1000 Genomes Project vis-à-vis global population data was studied to understand its role in drug response. Methods Joint genotyping approach was used to derive variants of GIH and ITU independently. SNPs of both these populations with significant allele frequency variation (minor allele frequency ≥ 0.05) with super-populations from the 1000 Genomes Project and gnomAD based on Chi-square distribution with p-value of ≤ 0.05 and Bonferroni’s multiple adjustment tests were identified. Population stratification and fixation index analysis was carried out to understand genetic differentiation. Functional annotation of variants was carried out using SnpEff, VEP and CADD score. Results Population stratification of VIP genes revealed four clusters viz., single cluster of GIH and ITU, one cluster each of East Asian, European, African populations and Admixed American was found to be admixed. A total of 13 SNPs belonging to ten pharmacogenes were identified to have significant allele frequency variation in both GIH and ITU populations as compared to one or more super-populations. These SNPs belong to VKORC1 (rs17708472, rs2359612, rs8050894) involved in Vitamin K cycle, cytochrome P450 isoforms CYP2C9 (rs1057910), CYP2B6 (rs3211371), CYP2A2 (rs4646425) and CYP2A4 (rs4646440); ATP-binding cassette (ABC) transporter ABCB1 (rs12720067), DPYD1 (rs12119882, rs56160474) involved in pyrimidine metabolism, methyltransferase COMT (rs9332377) and transcriptional factor NR1I2 (rs6785049). SNPs rs1544410 (VDR), rs2725264 (ABCG2), rs5215 and rs5219 (KCNJ11) share high fixation index (≥ 0.5) with either EAS/AFR populations. Missense variants rs1057910 (CYP2C9), rs1801028 (DRD2) and rs1138272 (GSTP1), rs116855232 (NUDT15); intronic variants rs1131341 (NQO1) and rs115349832 (DPYD) are identified to be ‘deleterious’. Conclusions Analysis of SNPs pertaining to pharmacogenes in GIH and ITU populations using population structure, fixation index and allele frequency variation provides a premise for understanding the role of genetic diversity in drug response in Asian Indians.
format	article
author	Neeraj Bharti Ruma Banerjee Archana Achalere Sunitha Manjari Kasibhatla Rajendra Joshi
author_facet	Neeraj Bharti Ruma Banerjee Archana Achalere Sunitha Manjari Kasibhatla Rajendra Joshi
author_sort	Neeraj Bharti
title	Genetic diversity of ‘Very Important Pharmacogenes’ in two South-Asian populations
title_short	Genetic diversity of ‘Very Important Pharmacogenes’ in two South-Asian populations
title_full	Genetic diversity of ‘Very Important Pharmacogenes’ in two South-Asian populations
title_fullStr	Genetic diversity of ‘Very Important Pharmacogenes’ in two South-Asian populations
title_full_unstemmed	Genetic diversity of ‘Very Important Pharmacogenes’ in two South-Asian populations
title_sort	genetic diversity of ‘very important pharmacogenes’ in two south-asian populations
publisher	PeerJ Inc.
publishDate	2021
url	https://doaj.org/article/f830bd248e5d4731844d7a9f9557d854
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Genetic diversity of ‘Very Important Pharmacogenes’ in two South-Asian populations

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