The analysis of GSTA1 promoter genetic and functional diversity of human populations

Abstract GSTA1 encodes a member of a family of enzymes that function to add glutathione to target electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. GSTA1 has several functional SNPs within its promoter region that are responsib...

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Autores principales:	Vid Mlakar, Patricia Huezo-Diaz Curtis, Marc Armengol, Victor Ythier, Isabelle Dupanloup, Khalil Ben Hassine, Laurence Lesne, Rabih Murr, Simona Jurkovic Mlakar, Tiago Nava, Marc Ansari
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3009698d325a4a0cbc6a555f80e7f449
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spelling	oai:doaj.org-article:3009698d325a4a0cbc6a555f80e7f4492021-12-02T11:37:21ZThe analysis of GSTA1 promoter genetic and functional diversity of human populations10.1038/s41598-021-83996-22045-2322https://doaj.org/article/3009698d325a4a0cbc6a555f80e7f4492021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83996-2https://doaj.org/toc/2045-2322Abstract GSTA1 encodes a member of a family of enzymes that function to add glutathione to target electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. GSTA1 has several functional SNPs within its promoter region that are responsible for a change in its expression by altering promoter function. This study aims to investigate distributions of GSTA1 promoter haplotypes across different human populations and to assess their impact on the expression of GSTA1. PHASE 2.1.1 was used to infer haplotypes and diplotypes of six GSTA1 promoter SNPs on 2501 individuals from 26 populations classified by the 1000 Genomes Project into five super-populations that included Africa (N = 660), America (N = 347), East Asia (N = 504), Europe (N = 502), and South Asia (N = 488). We used pairwise FST analysis to compare sub-populations and luciferase reporter assay (LRA) to evaluate the impact of each SNP on activation of transcription and interaction with other SNPs. The distributions of GSTA1 promoter haplotypes and diplotypes were significantly different among the different human populations. Three new promoter haplotypes were found in the African super-population. LRA demonstrated that SNPs at -52 and -69 has the most impact on GSTA1 expression, however other SNPs have a significant impact on transcriptional activity. Based on LRA, a new model of cis-elements interaction is presented. Due to the significant differences in GSTA1 diplotype population frequencies, future pharmacogenomics or disease-related studies would benefit from the inclusion of the complete GSTA1 promoter haplotype based on the newly proposed metabolic grouping derived from the LRA results.Vid MlakarPatricia Huezo-Diaz CurtisMarc ArmengolVictor YthierIsabelle DupanloupKhalil Ben HassineLaurence LesneRabih MurrSimona Jurkovic MlakarTiago NavaMarc AnsariNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Vid Mlakar Patricia Huezo-Diaz Curtis Marc Armengol Victor Ythier Isabelle Dupanloup Khalil Ben Hassine Laurence Lesne Rabih Murr Simona Jurkovic Mlakar Tiago Nava Marc Ansari The analysis of GSTA1 promoter genetic and functional diversity of human populations
description	Abstract GSTA1 encodes a member of a family of enzymes that function to add glutathione to target electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. GSTA1 has several functional SNPs within its promoter region that are responsible for a change in its expression by altering promoter function. This study aims to investigate distributions of GSTA1 promoter haplotypes across different human populations and to assess their impact on the expression of GSTA1. PHASE 2.1.1 was used to infer haplotypes and diplotypes of six GSTA1 promoter SNPs on 2501 individuals from 26 populations classified by the 1000 Genomes Project into five super-populations that included Africa (N = 660), America (N = 347), East Asia (N = 504), Europe (N = 502), and South Asia (N = 488). We used pairwise FST analysis to compare sub-populations and luciferase reporter assay (LRA) to evaluate the impact of each SNP on activation of transcription and interaction with other SNPs. The distributions of GSTA1 promoter haplotypes and diplotypes were significantly different among the different human populations. Three new promoter haplotypes were found in the African super-population. LRA demonstrated that SNPs at -52 and -69 has the most impact on GSTA1 expression, however other SNPs have a significant impact on transcriptional activity. Based on LRA, a new model of cis-elements interaction is presented. Due to the significant differences in GSTA1 diplotype population frequencies, future pharmacogenomics or disease-related studies would benefit from the inclusion of the complete GSTA1 promoter haplotype based on the newly proposed metabolic grouping derived from the LRA results.
format	article
author	Vid Mlakar Patricia Huezo-Diaz Curtis Marc Armengol Victor Ythier Isabelle Dupanloup Khalil Ben Hassine Laurence Lesne Rabih Murr Simona Jurkovic Mlakar Tiago Nava Marc Ansari
author_facet	Vid Mlakar Patricia Huezo-Diaz Curtis Marc Armengol Victor Ythier Isabelle Dupanloup Khalil Ben Hassine Laurence Lesne Rabih Murr Simona Jurkovic Mlakar Tiago Nava Marc Ansari
author_sort	Vid Mlakar
title	The analysis of GSTA1 promoter genetic and functional diversity of human populations
title_short	The analysis of GSTA1 promoter genetic and functional diversity of human populations
title_full	The analysis of GSTA1 promoter genetic and functional diversity of human populations
title_fullStr	The analysis of GSTA1 promoter genetic and functional diversity of human populations
title_full_unstemmed	The analysis of GSTA1 promoter genetic and functional diversity of human populations
title_sort	analysis of gsta1 promoter genetic and functional diversity of human populations
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3009698d325a4a0cbc6a555f80e7f449
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The analysis of GSTA1 promoter genetic and functional diversity of human populations

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