The Influence of Insulin-like Growth Factor Pathway Gene Polymorphisms on the Strength Training Response of Muscle Phenotypes in Older Adults

Title of dissertation: THE INFLUENCE OF INSULIN-LIKE GROWTH FACTOR PATHWAY GENE POLYMORPHISMS ON THE STRENGTH TRAINING RESPONSE OF MUSCLE PHENOTYPES IN OLDER ADULTS Brian Dudley Hand, Doctor of Philosophy, 2006 Dissertation directed by: Professor Ben F. Hurley Department of Kinesiology Strength training (ST) is considered an intervention of choice for the prevention and treatment of the adverse consequences of sarcopenia. Our group previously reported that the CA dinucleotide repeat polymorphism in the promoter region of the insulin-like growth factor 1 (IGF1) gene influenced the muscle strength response to ST in Caucasians. Other studies have shown that the insulin-like growth factor binding protein3 (IGFBP-3) is a modulator of IGF-1 in circulation and is present in skeletal muscle. The -202 polymorphism in the promoter region of the IGFBP3 gene has been shown to influence IGFBP-3 levels. In addition, there have been reports that IGF-1 and calcineurin are linked in a common pathway to induce skeletal muscle cell hypertrophy. A previous study has shown that an insertion/deletion (I/D) polymorphism in the gene encoding the regulatory subunit of calcineurin, calcineurin B, influences cardiac hypertrophy. To examine the influence of these IGF pathway gene polymorphisms on muscle mass and strength responses to ST, we studied 128 Caucasian and African American men and women before and after a 10-wk single-leg knee extension ST program. One repetition maximum strength (1 RM), muscle volume (MV), and muscle quality (MQ) were assessed at baseline and after 10 wk of ST. There was a significant combined gene effect, including both IGF1 main effect and IGF1 by calcineurin B (PPP3R1) gene by gene interaction effect, for change in strength with ST (P < 0.01). There was also a significant combined gene effect for IGF1 on change in MQ (P < 0.05). The gene by gene interaction of IGF1 and PPP3R1 by itself, approached significance for change in strength with ST (P = 0.07) and was right on the border of significance for change in MQ (P = 0.05). Moreover, PPP3R1 II homozygotes approached significance for a greater increase in MV with ST than PPP3R1 D-allele carriers (P = 0.06). There were no significant combined gene effect for PPP3R1 (i.e., PPP3R1 main effect combined with PPP3R1 by IGF1 interaction effect) for change in strength or MQ with ST. Also, there were no significant influences of the IGFBP3 polymorphism on muscle phenotypic responses to ST. These data extend our previous findings for IGF1 by indicating that IGF pathway gene polymorphisms may influence muscle phenotypic responses to ST in Caucasian and African American older men and women. THE INFLUENCE OF INSULIN-LIKE GROWTH FACTOR PATHWAY GENE POLYMORPHISMS ON THE STRENGTH TRAINING RESPONSE OF MUSCLE PHENOTYPES IN OLDER ADULTS By Brian Dudley Hand Dissertation submitted to the Faculty of the Graduate School of the University of Maryland, College Park in partial fulfillment of the requirements for the degree of Doctor of Philosophy 2006 Advisory Committee: Professor Ben F. Hurley, Chair Associate Professor Michael D. Brown Professor Larry W. Douglass Professor James H. Hagberg Assistant Professor Stephen M. Roth