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Glucocorticoid receptor (NR3C1) polymorphisms associate with obesity, muscle strength, and cortisol sensitivity. We examined associations among four NR3C1 polymorphisms and the muscle response to resistance training (RT). European-American adults (n = 602, 23.8±0.4yr) completed a 12 week unilateral arm RT program. Maximum voluntary contraction (MVC) assessed isometric strength (kg) and MRI assessed biceps size (cm2) pre- and post-resistance training. Subjects were genotyped for NR3C1 -2722G>A, -1887G>A, -1017T>C, and +363A>G. Men carrying the -2722G allele gained less relative MVC (17.3±1.2vs33.5±6.1%) (p = 0.010) than AA homozygotes; men with -1887GG gained greater relative MVC than A allele carriers (19.6±1.4vs13.2±2.3%) (p = 0.016). Women carrying the -1017T allele gained greater relative size (18.7±0.5vs16.1±0.9%) (p = 0.016) than CC homozygotes. We found sex-specific NR3C1 associations with the muscle strength and size response to RT. Future studies should investigate whether these associations are partially explained by cortisol's actions in muscle tissue as they interact with sex differences in cortisol production.

Objectives: The purpose of this study was to determine the gender-specific independent association between muscular strength and cardiometabolic risk clustering in a large cohort (n = 1421) of children., Methods: Principal component analysis was used to determine the pattern of risk clustering and to derive a continuous aggregate score (MetScore) from various cardiometabolic risk components: percent body fat (%BF), fasting glucose, blood pressure, plasma triglycerides levels, and HDL-cholesterol. Gender-stratified risk and MetScore were assessed by using general linear models and logistic regression for differences between strength tertiles, as well as independent associations with age, BMI, estimated cardiorespiratory fitness (CRF), physical activity, and muscular strength (normalized for body mass)., Results: In both boys (n = 670) and girls (n = 751), there were significant differences in cardiometabolic profiles across strength tertiles, such that stronger adolescents had lower overall risk. Age, BMI, cardiorespiratory fitness, physical activity participation, and strength were all individually correlated with multiple risk components, as well as the overall MetScore. However, in the adjusted model, only BMI (β = 0.30), physical inactivity (β = 0.30), and normalized strength capacity (β = -1.5) emerged as significant (P < .05) predictors of MetScore. %BF was the strongest loading coefficient within the principal component analysis-derived MetScore outcome., Conclusions: Normalized strength is independently associated with lower cardiometabolic risk in boys and girls. Moreover, %BF was associated with all cardiometabolic risk factors and carried the strongest loading coefficient. These findings bolster the importance of early strength acquisition and healthy body composition in childhood.

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.

Baseline muscle size and muscle adaptation to exercise are traits with high variability across individuals. Recent research has implicated several chemokines and their receptors in the pathogenesis of many conditions that are influenced by inflammatory processes, including muscle damage and repair. One specific chemokine, chemokine (C-C motif) ligand 2 (CCL2), is expressed by macrophages and muscle satellite cells, increases expression dramatically following muscle damage, and increases expression further with repeated bouts of exercise, suggesting that CCL2 plays a key role in muscle adaptation. The present study hypothesizes that genetic variations in CCL2 and its receptor (CCR2) may help explain muscle trait variability. College-aged subjects [n = 874, Functional Single-Nucleotide Polymorphisms Associated With Muscle Size and Strength (FAMUSS) cohort] underwent a 12-wk supervised strength-training program for the upper arm muscles. Muscle size (via MR imaging) and elbow flexion strength (1 repetition maximum and isometric) measurements were taken before and after training. The study participants were then genotyped for 11 genetic variants in CCL2 and five variants in CCR2. Variants in the CCL2 and CCR2 genes show strong associations with several pretraining muscle strength traits, indicating that inflammatory genes in skeletal muscle contribute to the polygenic system that determines muscle phenotypes. These associations extend across both sexes, and several of these genetic variants have been shown to influence gene regulation.

Previous studies have reported associations of polymorphisms in the IGF1 gene with phenotypes of body composition (BC). The purpose of this study was to identify phenotypes of BC and physical function that were associated with the IGF1 promoter polymorphism (rs35767, -C1245T). Subjects from the Health, Aging, and Body Composition Study, white males and females (n = 925/836) and black males and females (533/705) aged 70-79 years were genotyped for the polymorphism. Phenotypes of muscle size and function, bone mineral density, and BC were analyzed for associations with this polymorphism. To validate and compare these findings, a cohort of young (mean age = 24.6, SD = 5.9) white men and women (n = 173/296) with similar phenotypic measurements were genotyped. An association with BC was identified in elderly females when significant covariates (physical activity, age, smoking status, body mass index) were included. White women with C/C genotype had 3% more trunk fat and 2% more total fat than those with C/T (P < 0.05). Black women with C/C genotype had 3% less total lean mass and 3% less muscle mass than their T/T counterparts (P < 0.05). Associations were identified with muscle strength in white women (P < 0.01) that were in agreement with the C/C genotype having lower muscle function. Thus, in an elderly population but not a young population, a polymorphism in the IGF1 gene may be predictive of differences in body composition, primarily in black females.

The present study examined associations between the ciliary neurotrophic factor (CNTF) 1357 G --> A polymorphism and the muscle strength response to a unilateral, upper arm resistance-training (RT) program among healthy, young adults. Subjects were 754 Caucasian men (40%) and women (60%) who were genotyped and performed a training program of the nondominant (trained) arm with the dominant (untrained) arm as a comparison. Peak elbow flexor strength was measured with one repetition maximum, isometric strength with maximum voluntary contraction, and bicep cross-sectional area with MRI in the trained and untrained arms before and after training. Women with the CNTF GG genotype gained more absolute isometric strength, as measured by MVC (6.5 +/- 0.3 vs. 5.2 +/- 0.5 kg), than carriers of the CNTF A1357 allele in the trained arm pre- to posttraining (P < 0.05). No significant associations were seen in men. Women with the CNTF GG genotype gained more absolute dynamic (1.0 +/- 0.1 vs. 0.6 +/- 0.1 kg) and allometric (0.022 +/- 0.0 vs. 0.015 +/- 0.0 kg/kg(-0.67)) strength, as measured by 1 RM, than carriers of the CNTF A1357 allele in the untrained arm pre- to posttraining (P < 0.05). No significant associations were seen in men. No significant associations, as measured by cross-sectional area, were seen in men or women. The CNTF 1357 G --> A polymorphism explains only a small portion of the variability in the muscle strength response to training in women.

The purpose of this study was to assess the association of age with muscle mass and strength in a group of young adults before and after 12 weeks of progressive resistance training. Eight hundred twenty-six young males and females (age 24.34 +/- 5.69 yr, range 18-39 yr) completed a strictly supervised 12-week unilateral resistance training program of the nondominant arm. Isometric (maximal voluntary contraction [MVC]) and dynamic strength (1 repetition maximum [1RM]) of the elbow flexors and cross-sectional area (CSA) of the biceps-brachii using magnetic resonance imaging (MRI) scans were measured before and after training. Pearson correlation coefficients were calculated for size and strength variables and age. In addition, the cohort was divided into groups according to decade of life and differences assessed by analysis of variance. Age correlated significantly and positively with all pretraining measures of muscle size and strength (CSA: r = 0.191, p < 0.001; MVC: r = 0.109, p = 0.002; 1RM: r = 0.109, p = 0.002). Age was not related to the training-induced changes in CSA or MVC but was negatively associated with the change in 1RM (r = -0.217, p < 0.001). The study indicates that age does have a significant positive relationship with muscle size and strength in untrained young adults. Although age was negatively associated with improvements in 1RM, the effect of age was small relative to the improvements induced through resistance training, thus suggesting age does not limit response to training in any practical way during early adulthood.

Overweight and obesity result in musculoskeletal impairments that limit exercise capacity. We examined if the muscle strength and size response to resistance training (RT) differed among 687 young (mean +/- SEM, 24.2 +/- 0.2 years) overweight and obese (OW) compared to normal weight (NW) adults as denoted by the body mass index (BMI). Subjects were 449 NW (22.0 +/- 0.1 kg.m(-2), 23.4 +/- 0.3 years) and 238 OW (29.2 +/- 0.2 kg.m(-2), 25.6 +/- 0.4 years) men (n = 285) and women (n = 402) who underwent 12 weeks (2 d.wk(-1)) of RT of the nondominant arm. Maximum voluntary contraction (MVC) and 1 repetition maximum (1RM) assessed peak elbow flexor strength. Magnetic resonance imaging measured the biceps muscle cross sectional area (CSA). Multiple dependent variable analysis of covariance tested if muscle strength and size differed among BMI groups pre-, post-, and pre-to-post-RT. Overweight and obese had greater MVC, 1RM, and CSA than NW pre- and post-RT (p < 0.001). Maximum voluntary contraction and 1RM gains were not different between BMI groups pre- to post-RT (p >or= 0.05). When adjusted for baseline values, NW had greater relative MVC (21.2 +/- 1.0 vs. 17.4 +/- 1.4%) and 1RM (54.3 +/- 1.5 vs. 49.0 +/- 2.0%) increases than OW (p < 0.05). Normal weight also had greater allometric MVC (0.48 +/- 0.02 kg.kg(-0.67) vs. 0.40 +/- 0.03 kg.kg(-0.67)) and 1RM (0.25 +/- 0.00 vs. 0.22 +/- 0.01 kg.kg(-0.67)) gains than OW (p < 0.05). CSA gains were greater among OW than NW (3.6 +/- 0.2 vs. 3.2 +/- 0.1 cm(2)) (p < 0.001); however, relative CSA increases were not different between BMI groups (19.4 +/- 0.5 vs. 18.4 +/- 0.7%) (p >or= 0.05). Despite similar relative muscle size increases, relative and allometic strength gains were less among OW than NW. These findings indicate the short-term relative and allometric muscle strength response to RT may be attenuated among adults who are overweight and obese.

Objective. We examined the influence of missense polymorphism, endothelial nitric oxide synthase (NOS3) + 894 G>T (rs1799983), on habitual physical activity (PA) and the muscle strength response to resistance training (RT). Methods. Men (n = 354) and women (n = 424; 24.3 ± 8.0 yr) were genotyped. Subjects reported hr/wk in vigorous and light intensity PA and sitting on the Paffenbarger PA questionnaire. One repetitionmaximum assessedmuscle strength. Multivariable and repeated measures ANCOVA tested differences among NOS3 +894 G>T and PA and RT phenotypes by gender. Results. hr/wk in vigorous intensity PA (5.4 ± 1.2 versus 8.3 ± 0.4; P = 0.019), more hr/wk in light intensity PA (42.1 ± 2.4 versus 35.8 ± 0.7; P = 0.011), and less hr/wk sitting (37.6 ± 2.8 versus 45.8 ± 0.9; P = 0.006) than those with the G allele. Women with NOS3 +894 TT gained more absolute (4.4 ± 0.3 versus 3.7 ± 0.8 kg; P = 0.013) and relative (78.3 ± 5.8 versus 61.9 ± 1.8%; P = 0.007) strength than those with the G allele. Conclusions. NOS3 +894 G>T associated with PA among men and women and the muscle strength response to RT among women only. Our findings indicate the need for prospective studies examining the influence of NOS3 variants on PA and the muscle response to RT as well as elucidating underlying mechanistic pathways for the associations observed. [ABSTRACT FROM AUTHOR]

Purpose: To assess strength, size, and muscle quality differences between younger and older males and females in response to training. Methods: The bicep and tricep of the non-dominant arm were trained for twelve weeks in younger and older males and females (n = 41). The bicep of both arms were assessed pre and post for muscle strength using one-repetition maximum (1 RM) testing, and size using magnetic resonance imaging (MRI). Results: Strength (p < 0.05), mCSA (p < 0.05), and 1 RM MQ (p < 0.00) increased in response to training in all subjects regardless of age or gender. Younger and older subjects had similar increases in strength (45.49 ± 15.30% vs. 42.67 ± 26.67% respectively), mCSA (16.22 ± 7.98% vs. 19.17 ± 6.19% respectively), and 1RM MQ (25.73 ± 15.76 vs. 19.67 ± 20.66 respectively). Women increased their strength (55.59 ± 19.45% vs. 32.87 ± 15.66% p < 0.00 respectively), size (20.36 ± 6.29% vs. 14.72 ± 7.28% p < 0.02 respectively), and 1 RM MQ (29.74 ± 18.33% vs. 16.30 ± 15.59% p <.02) more than men. In comparing age and gender, younger females increased their strength more than older males (56.42 ± 12.92% vs. 29.17 ± 21.8% p <.02 respectively). Older females also increased their strength more than older males (54.68 ± 25.73 vs. 29.17 ± 21.80% respectively). Younger females increased their 1 RM MQ more than older males (.18 ± .08 kg/cm vs. .06 ± .08 kg/cm p <.02 respectively). Conclusion: Strength and mCSA increases similarly in older and younger subjects. However, the overall strength and quality of the muscle seems to improve more in women than in men. [ABSTRACT FROM AUTHOR]

The α-actinin 3 (ACTN3) gene encodes a protein of the Z disk of myofibers, and a polymorphism of ACTN3 results in complete loss of the protein. The ACTN3 genotype (R577X) has been found to be associated with performance in Australian elite athletes (Yang N, MacArthur DG, Gulbin JP, Hahn AG, Beggs AH, Easteal S, and North K. Am J Hum Genet 73: 627-631, 2003). We studied associations between ACTN3 genotype and muscle size [cross-sectional area of the biceps brachii via magnetic resonance imaging (MRI)] and elbow flexor isometric (MVC) and dynamic [1-repetition maximum (1-RM)] strength in a large group of men (N = 247) and women (N = 355) enrolled in a 12-wk standardized elbow flexor/ extensor resistance training program of the nondominant arm at one of eight study centers. We found no association between ACTN3 R577X genotype and muscle phenotype in men. However, women homozygous for the ACTN3 577X allele (XX) had lower baseline MVC compared with heterozygotes (P < 0.05) when adjusted for body mass and age. Women homozygous for the mutant allele (577X) demonstrated greater absolute and relative 1-RM gains compared with the homozygous wild type (RR) after resistance training when adjusted for body mass and age (P < 0.05). There was a trend for a dose-response with genotype such that gains were greatest for XX and least for RR. Significant associations were validated in at least one ethnic subpopulation (Caucasians, Asians) and were independent of training volume. About 2% of baseline MVC and of 1-RM strength gain after training were attributable to ACTN3 genotype (likelihood-ratio test P value, P = 0.01), suggesting that ACTN3 is one of many genes contributing to genetic variation in muscle performance and adaptation to exercise. [ABSTRACT FROM AUTHOR]

Introduction: There is an association between strength and health among adolescents, yet, what remains to be determined is sex-specific cut points for low strength in the detection of risk in this population. The purpose of this study was to determine thresholds of low grip strength in a large cohort (N=1,326) of adolescents.Methods: All data were collected between 2005 and 2008, and analyzed in 2014-2015. A cardiometabolic risk score (MetScore) was computed from the following components: percent body fat, fasting glucose, blood pressure, plasma triglyceride levels, and high-density lipoprotein cholesterol. A high-risk cardiometabolic phenotype was characterized as ≥75th percentile of the MetScore. Conditional inference tree analyses were used to identify sex-specific, low normalized strength (grip strength/body mass) thresholds and risk categories.Results: Lower strength was independently associated with increased odds of the high-risk cardiometabolic phenotype, such that for every 5% decrement of normalized strength, there were 1.48 and 1.45 increased odds (p<0.001) for boys and girls, even after adjusting for cardiorespiratory fitness and physical activity. Conditional tree analysis revealed a high-risk threshold for boys (≤0.33) and girls (≤0.28), as well as an intermediate threshold (boys, >0.33 and ≤0.45; girls, >0.28 and ≤0.36).Conclusions: These sex-specific thresholds of low strength can be incorporated into a clinical setting for identifying adolescents that would benefit from lifestyle interventions to improve muscular fitness and reduce cardiometabolic risk. [ABSTRACT FROM AUTHOR]

The article examines associations among the angiotensin I-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism and the response to a 12-week unilateral, upper-arm resistance training program in the trained and untrained arms. The test subjects used in the study were 631 white men and women. The ACE ID genotype was in Hardy-Weinberg equilibrium with frequencies of 23.1, 46.1 and 30.8% for ACE II, ID and DD respectively. Maximum voluntary contraction and one-repetition maximum assessed peak elbow flexor muscle strength.