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

Article Article scientifique Article The analysis of GSTA1 promoter genetic and functional diversity of human populations eng 2021-03-03 2021-03-03 author Mlakar Vid 842534 author Curtis Patricia 692141 author Armengol Marc 0000-0001-5206-9139 864612 author Ythier Victor 0000-0003-4389-3200 907859 author Dupanloup De Ceuninck Isabelle 27649 author Ben Hassine Khalil 779097 author Lesne Laurence 62499 author Murr Rabih 827872 author Mlakar Simona 856065 author Nava Tiago 863338 author Ansari Djaberi Marc Georges 61572 5038 10.1038/s41598-021-83996-2 33658540 2045-2322 PMC7930039 https://www.nature.com/articles/s41598-021-83996-2 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. Dewey 576.5 Dewey 618 Swiss National Science Foundation Personalizing busulfan based myeloablative conditioning regimens prior to allogenic hematopoietic stem cell transplantation in children 320030_153389 CH Project funding OAK foundation OCAY-17-642 135 Département de médecine génétique et développement 21D 58 Département de pédiatrie, gynécologie et obstétrique 223 false 564 Oncologie et hématologie pédiatriques 907 Scientific reports 11 1 e6e424eb-233e-4c49-b9c6-7d3d76ef8304 Article (Published version) Public Article-scientifique-from-europePmc.pdf 1370257 application/pdf CC BY-4.0 d1feb12d-2249-4a57-93f3-747b462d219d Appendix Public 41598_2021_83996_MOESM1_ESM.pdf 773001 application/pdf openAccess Faculté de médecine / Section de médecine fondamentale / Département de médecine génétique et développement Faculté de médecine / Section de médecine clinique / Département de pédiatrie, gynécologie et obstétrique

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The analysis of GSTA1 promoter genetic and functional diversity of human populations	Scientific reports			2021	284	325

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Armengol, Marc