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 efect
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 stratifed 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 ftness, 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 fndings 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 signifcant impact on responsiveness to exercise interventions.The South African Medical Research Council (SAMRC), the National Research Foundation professional development program (PDP), Tuthuka and the International Atomic Energy agency.https://www.nature.com/srepdm2022Obstetrics and Gynaecolog
