A pilot investigation of genetic and epigenetic variation of FKBP5 and response to exercise intervention in African women with obesity

Abstract We investigated gluteal (GSAT) and abdominal subcutaneous adipose tissue (ASAT) DNA methylation of FKBP5 in response to a 12-week intervention in African women with obesity, as well as the effect of the rs1360780 single nucleotide polymorphism (SNP) on FKBP5 methylation, gene expression and...

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Main Authors: Tarryn Willmer, Amberly Oosthuizen, Stephanie Dias, Amy E. Mendham, Julia H. Goedecke, Carmen Pheiffer
Format: Article
Language:English
Published: Nature Portfolio 2022-07-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-022-15678-6
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author Tarryn Willmer
Amberly Oosthuizen
Stephanie Dias
Amy E. Mendham
Julia H. Goedecke
Carmen Pheiffer
author_facet Tarryn Willmer
Amberly Oosthuizen
Stephanie Dias
Amy E. Mendham
Julia H. Goedecke
Carmen Pheiffer
author_sort Tarryn Willmer
collection DOAJ
description Abstract We investigated gluteal (GSAT) and abdominal subcutaneous adipose tissue (ASAT) DNA methylation of FKBP5 in response to a 12-week intervention in African women with obesity, as well as the effect of the rs1360780 single nucleotide polymorphism (SNP) on FKBP5 methylation, gene expression and post-exercise training adaptations in obesity and metabolic related parameters. Exercise (n = 19) participants underwent 12-weeks of supervised aerobic and resistance training while controls (n = 12) continued their usual behaviours. FKBP5 methylation was measured in GSAT and ASAT using pyrosequencing. SNP and gene expression analyses were conducted using quantitative real-time PCR. Exercise training induced FKBP5 hypermethylation at two CpG dinucleotides within intron 7. When stratified based on the rs1360780 SNP, participants with the CT genotype displayed FKBP5 hypermethylation in GSAT (p < 0.05), and ASAT displayed in both CC and CT carriers. CC allele carriers displayed improved cardiorespiratory fitness, insulin sensitivity, gynoid fat mass, and waist circumference (p < 0.05) in response to exercise training, and these parameters were attenuated in women with the CT genotype. These findings provide a basis for future studies in larger cohorts, which should assess whether FKBP5 methylation and/or genetic variants such as the rs1360780 SNP could have a significant impact on responsiveness to exercise interventions.
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spelling doaj.art-7e4abf94db554ba980bbfc7d129d35d82022-12-22T03:00:47ZengNature PortfolioScientific Reports2045-23222022-07-0112111210.1038/s41598-022-15678-6A pilot investigation of genetic and epigenetic variation of FKBP5 and response to exercise intervention in African women with obesityTarryn Willmer0Amberly Oosthuizen1Stephanie Dias2Amy E. Mendham3Julia H. Goedecke4Carmen Pheiffer5Biomedical Research and Innovation Platform, South African Medical Research CouncilBiomedical Research and Innovation Platform, South African Medical Research CouncilBiomedical Research and Innovation Platform, South African Medical Research CouncilSouth African Medical Research Council/WITS Developmental Pathways for Health Research Unit (DPHRU), Department of Paediatrics, School of Clinical Medicine, Faculty of Health Sciences, University of the WitwatersrandDivision of Physiological Sciences, Health Through Physical Activity, Lifestyle and Sport Research Centre (HPALS), Department of Human Biology, Faculty of Health Sciences, FIMS International Collaborating Centre of Sports Medicine, University of Cape TownBiomedical Research and Innovation Platform, South African Medical Research CouncilAbstract We investigated gluteal (GSAT) and abdominal subcutaneous adipose tissue (ASAT) DNA methylation of FKBP5 in response to a 12-week intervention in African women with obesity, as well as the effect of the rs1360780 single nucleotide polymorphism (SNP) on FKBP5 methylation, gene expression and post-exercise training adaptations in obesity and metabolic related parameters. Exercise (n = 19) participants underwent 12-weeks of supervised aerobic and resistance training while controls (n = 12) continued their usual behaviours. FKBP5 methylation was measured in GSAT and ASAT using pyrosequencing. SNP and gene expression analyses were conducted using quantitative real-time PCR. Exercise training induced FKBP5 hypermethylation at two CpG dinucleotides within intron 7. When stratified based on the rs1360780 SNP, participants with the CT genotype displayed FKBP5 hypermethylation in GSAT (p < 0.05), and ASAT displayed in both CC and CT carriers. CC allele carriers displayed improved cardiorespiratory fitness, insulin sensitivity, gynoid fat mass, and waist circumference (p < 0.05) in response to exercise training, and these parameters were attenuated in women with the CT genotype. These findings provide a basis for future studies in larger cohorts, which should assess whether FKBP5 methylation and/or genetic variants such as the rs1360780 SNP could have a significant impact on responsiveness to exercise interventions.https://doi.org/10.1038/s41598-022-15678-6
spellingShingle Tarryn Willmer
Amberly Oosthuizen
Stephanie Dias
Amy E. Mendham
Julia H. Goedecke
Carmen Pheiffer
A pilot investigation of genetic and epigenetic variation of FKBP5 and response to exercise intervention in African women with obesity
Scientific Reports
title A pilot investigation of genetic and epigenetic variation of FKBP5 and response to exercise intervention in African women with obesity
title_full A pilot investigation of genetic and epigenetic variation of FKBP5 and response to exercise intervention in African women with obesity
title_fullStr A pilot investigation of genetic and epigenetic variation of FKBP5 and response to exercise intervention in African women with obesity
title_full_unstemmed A pilot investigation of genetic and epigenetic variation of FKBP5 and response to exercise intervention in African women with obesity
title_short A pilot investigation of genetic and epigenetic variation of FKBP5 and response to exercise intervention in African women with obesity
title_sort pilot investigation of genetic and epigenetic variation of fkbp5 and response to exercise intervention in african women with obesity
url https://doi.org/10.1038/s41598-022-15678-6
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