AUTHOR=Lewis Lauren S. , Huffman Kim M. , Smith Ira J. , Donahue Mark P. , Slentz Cris A. , Houmard Joseph A. , Hubal Monica J. , Hoffman Eric P. , Hauser Elizabeth R. , Siegler Ilene C. , Kraus William E. 

TITLE=Genetic Variation in Acid Ceramidase Predicts Non-completion of an Exercise Intervention

JOURNAL=Frontiers in Physiology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.00781

DOI=10.3389/fphys.2018.00781

ISSN=1664-042X

ABSTRACT=<p>Genetic variation is associated with a number of lifestyle behaviours; it may be associated with adherence and individual responses to exercise training. We tested single nucleotide polymorphisms (SNPs) in the acid ceramidase gene (<italic>ASAH1</italic>) for association with subject adherence and physiologic benefit with exercise training in two well-characterised randomised, controlled 8-month exercise interventions: STRRIDE I (<italic>n</italic> = 239) and STRRIDE II (<italic>n</italic> = 246). Three <italic>ASAH1</italic> non-coding SNPs in a linkage disequilibrium block were associated with non-completion: rs2898458(G/T), rs7508(A/G), and rs3810(A/G) were associated with non-completion in both additive (OR = 1.8, 1.8, 2.0; <italic>P</italic> &lt; 0.05 all) and dominant (OR = 2.5, 2.6, 3.5; <italic>P</italic> &lt; 0.05 all) models; with less skeletal muscle <italic>ASAH</italic> expression (<italic>p</italic> &lt; 0.01) in a subset (<italic>N</italic> = 60); and poorer training response in cardiorespiratory fitness (peak VO<sub>2</sub> change rs3810 <italic>r</italic><sup>2</sup> = 0.29, <italic>P</italic> = 0.04; rs2898458 <italic>r</italic><sup>2</sup> = 0.29, <italic>P</italic> = 0.08; rs7508 <italic>r</italic><sup>2</sup> = 0.28, <italic>p</italic> = 0.09); and similar in direction and magnitude in both independent exploratory and replication studies. Adherence to exercise may be partly biologically and genetically moderated through metabolic regulatory pathways participating in skeletal muscle adaptation to exercise training.</p>