Variants of the Ankyrin Repeat Domain 6 Gene (ANKRD6) and Muscle and Physical Activity Phenotypes Among European-Derived American Adults

Abstract

Ankyrin repeat domain 6 (ANKRD6) is a ubiquitous protein that associates with early development in mammals and is highly expressed in the brain, spinal cord, and heart of humans. We examined the role of 8 ANKRD6 single-nucleotide polymorphisms (SNPs) on muscle performance and habitual physical activity (PA). Single-nucleotide polymorphisms were 545 T>A (rs9362667), 485 M>L (rs61736690), 233 T>M (rs2273238), 128 I>L (rs3748085), 631 P>L (rs61739327), 122 Q>E (rs16881983), 197805 G>A (rs9344950), and 710 L>X (NOVEL). This study consisted of 922 healthy, untrained, European-derived American men (n = 376, 23.6 ± 0.3 years, 25.0 ± 0.2 kg·m−2) and women (n = 546, 23.2 ± 0.2 years, 24.0 ± 0.2 kg·m−2). Muscle strength (maximum voluntary contraction [MVC] and 1 repetition maximum [1RM]) and size (cross-sectional area [CSA]) were assessed before and after 12 weeks of unilateral resistance training (RT). A subsample (n = 536, 23.4 ± 0.2 years, 24.6 ± 0.2 kg·m−2) completed the Paffenbarger Physical Activity Questionnaire. Associations among ANKRD6 genotypes and muscle phenotypes were tested with repeated measure analysis of covariance (ANCOVA) and PA phenotypes with multivariate ANCOVA, with age and body mass index as covariates. ANKRD6 122 Q>E was associated with increased baseline biceps CSA. ANKRD6 545 A>T and ANKRD6 710 L>X were associated with increased 1RM and MVC in response to RT, respectively. ANKRD6 631 P>L was associated with increased biceps CSA response to RT and time spent in moderate-intensity PA among the total sample and women. ANKRD6 genetic variants were associated with the muscle size and strength response to RT and habitual PA levels. Further research is needed to validate our results and explore mechanisms for the associations we observed.

Heterogeneity in resistance training-induced muscle strength and mass responses in men and women of different ages

“…In previous studies with healthy human subjects, e.g., several genetic variations (Riechman et al 2004;Devaney et al 2009;Walsh et al 2012;Van Deveire et al 2012), differences in skeletal muscle gene Raue et al 2012;Phillips et al 2013) and microRNA expression (Davidsen et al 2011), phosphorylation status of signaling proteins (Mayhew et al 2011;Mitchell et al 2013), androgen receptor concentrations (Ahtiainen et al 2011;Mitchell et al 2013), and satellite cell count (Petrella et al 2008) have been suggested to segregate high and low responders to RTinduced muscle hypertrophy. The physiological aspects of individual variation in phenotype responses to RT are apparently very complex phenomena and more studies specifically focused on high and low responders are required to reveal unambiguously the mechanisms of individual differences in RT-induced adaptations.…”

Molecular Regulation of Exercise-Induced Muscle Fiber Hypertrophy

“…The majority of published literature on MARPs in muscle hypertrophy is focused on cardiac muscle. However, it is noteworthy that polymorphic variants of Ankrd6 in humans are associated with skeletal muscle size and the magnitude of RT-induced muscle hypertrophy (Van Deveire et al 2012). Cumulatively, the findings suggest that these sarcomere-related proteins may play a role in RT hypertrophy signaling, although more work is needed.…”

Endothelial Nitric Oxide Synthase (NOS3) +894 G>T Associates with Physical Activity and Muscle Performance among Young Adults

“…Thus, it appears NOS3 +894 G>T may habitually influence the preference of light PA, vigorous PA and sitting and the strength gains in women that can result from an RT program. These findings suggest NOS3 +894 G>T may be important to consider for a personalized approach to exercise prescription along with a growing number of genetic variants that have been reported to be associated with muscle performance [15,[24][25][26][27] and habitual PA [21,[28][29][30][31][32]. For example, when recommending exercise to adults for its overall health benefits, the NOS3 +894 G>T and PA intensity dependent genotype differences we found could be considered when counseling people to become more physically active due to what appears to be a genetic predisposition to prefer light over vigorous intensity PA among those with the TT genotype.…”

“…The experimental design of FAMuSS has been described elsewhere [6,[15][16][17][18][19][20][21]. The institutional review boards from the 10 institutions involved with the study approved the study protocol and informed consent was obtained from all individuals prior to enrollment.…”