Association of interleukin-15 protein and interleukin-15 receptor genetic variation with resistance exercise training responses

1 Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15260; and 2 Department of Kinesiology, University of Maryland, College Park, Maryland 20742 Submitted 6 May 2004 ; accepted in final form 16 July 2004 Interleukin-15 (IL-15) is an anabolic cytokine that is produced in skeletal muscle and directly affects muscle anabolism in animal and in vitro models. The contribution of IL-15 variability in muscle responses to 10 wk of resistance exercise training in young men and women was examined by measuring acute and chronic changes in IL-15 protein in plasma and characterizing genetic variation in the IL-15 receptor- gene (IL15RA). Participants trained 3 days a week at 75% of one repetition maximum, performing three sets (6–10 repetitions) of 13 resistance exercises. Plasma IL-15 protein was significantly increased ( P < 0.05) immediately after acute resistance exercise but did not change with training and was not associated with variability in muscle responses with training. A single nucleotide polymorphism in exon 7 of IL15RA was strongly associated with muscle hypertrophy and accounted for 7.1% of the variation in regression modeling. A polymorphism in exon 4 was also independently associated with muscle hypertrophy and accounted for an additional 3.5% of the variation in hypertrophy. These results suggest that IL-15 is an important mediator of muscle mass response to resistance exercise training in humans and that genetic variation in IL15RA accounts for a significant proportion of the variability in this response. IL-15; strength; skeletal muscle; muscle quality Address for reprint requests and other correspondence: S. E. Riechman, A300 Crabtree Hall, University of Pittsburgh, Pittsburgh, PA 15260 (E-mail: riechman{at}helix.hgen.pitt.edu )