Myostatin and Follistatin Polymorphisms Interact with Muscle Phenotypes and Ethnicity

Department of Kinesiology, University of Connecticut, Storrs, CT 06269-2101, USA.
Medicine &amp Science in Sports &amp Exercise (Impact Factor: 3.98). 04/2009; 41(5):1063-1071. DOI: 10.1249/MSS.0b013e3181930337
Source: PubMed


Purpose: We examined associations among myostatin (MSTN) 2379 A > G and 163 G > A and follistatin (FST) -5003 A > T and -833 G > T single nucleotide polymorphisms (SNP) on the muscle size and the strength response to resistance training (RT).
Methods: Subjects (n = 645, age = 24.1 ± 0.2 yr, body mass index [BMI] = 24.2 ± 0.2 kg·m-2) self-disclosed themselves as Caucasian (78.9%), African American (3.6%), Asian (8.4%), Hispanic (5.0%), or Other (4.2%). They were genotyped for MSTN 2379 A > G (n = 645), MSTN 163 G > A (n = 639), FST -5003 A > T (n = 580), and FST -833 G > T (n = 603). We assessed dynamic (one repetition maximum [1RM]) and isometric (maximum voluntary contraction [MVC]) muscle strength and size (cross-sectional area [CSA]) of the elbow flexors before and after 12 wk of unilateral upper-arm RT. Repeated-measures ANCOVA tested associations among genetic variants and muscle phenotypes with age and BMI as covariates.
Results: Baseline MVC was greater among African Americans who were carriers of the MSTN G2379 allele (AG/GG, n = 15) than the A2379A homozygotes (n = 8; 64.2 ± 6.8 vs 49.8 ± 8.7 kg). African Americans who were carriers of the FST T-5003 allele (n = 12) had greater baseline 1RM (11.9 ± 0.7 vs 8.8 ± 0.5 kg) and CSA (24.4 ± 1.3 vs 19.1 ± 1.2 cm2) than African Americans with the A-5003A genotype (n = 14; P < 0.05). No MSTN or FST genotype and muscle phenotype associations were found among the other ethnic groups (P ≥ 0.05).
Conclusion: MSTN 2379 A > G and FST -5003 A > T were associated with baseline muscle strength and size among African Americans only. These ethnic-specific associations are hypothesis generating and should be confirmed in a larger sample of African Americans.

Download full-text


Available from: Paul S Visich, Oct 03, 2015
65 Reads
  • Source
    • "However, the following observations suggest that MSTN expression may affect athletic performance: (a) Resistance training results in varying degrees of decreased MSTN expression (Walker et al. 2004; Jespersen et al. 2009). (b) MSTN genotypes were associated with baseline muscle strength and size in a small sample of African-Americans (Kostek et al. 2009). (c) MSTN genotype was associated with the ability to produce " peak " power during muscle contractions during stationary jumping in a population of young, nonathletic Caucasian men in Spain (Santiago et al. 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Historical events have produced an ideologically charged atmosphere in the USA surrounding the potential influences of innate variation on athletic performance. We tested the hypothesis that scientific studies of the role of innate variation in athletic performance were less likely to have authors with USA addresses than addresses elsewhere because of this cultural milieu. Using scientometric data collected from 290 scientific papers published in peer-reviewed journals from 2000-2012, we compared the proportions of authors with USA addresses with those that listed addresses elsewhere that studied the relationships between athletic performance and (a) prenatal exposure to androgens, as indicated by the ratio between digits 2 and 4, and (b) the genotypes for angiotensin converting enzyme, α-actinin-3, and myostatin; traits often associated with athletic performance. Authors with USA addresses were disproportionately underrepresented on papers about the role of innate variation in athletic performance. We searched NIH and NSF databases for grant proposals solicited or funded from 2000-2012 to determine if the proportion of authors that listed USA addresses was associated with funding patterns. NIH did not solicit grant proposals designed to examine these factors in the context of athletic performance and neither NIH nor NSF funded grants designed to study these topics. We think the combined effects of a lack of government funding and the avoidance of studying controversial or non-fundable topics by USA based scientists are responsible for the observation that authors with USA addresses were underrepresented on scientific papers examining the relationships between athletic performance and innate variation.
    SpringerPlus 06/2014; 3(1):307. DOI:10.1186/2193-1801-3-307
  • Source
    • "The FAMuSS group has reported genetic associations in several growth related genes in relation to both baseline and posttraining muscle traits [15, 20, 21]. Skeletal muscle growth and protein synthesis are controlled by several key signaling pathways, such as the phosphatidylinositol-3-kinase (PI3 K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The purpose of the Functional Single Nucleotide Polymorphisms Associated with Human Muscle Size and Strength study or FAMuSS was to identify genetic factors that dictated the response of health-related fitness phenotypes to resistance exercise training (RT). The phenotypes examined were baseline muscle strength and muscle, fat, and bone volume and their response to RT. FAMuSS participants were 1300 young (24 years), healthy men (42%) and women (58%) that were primarily of European-American descent. They were genotyped for ~500 polymorphisms and completed the Paffenbarger Physical Activity Questionnaire to assess energy expenditure and time spent in light, moderate, and vigorous intensity habitual physical activity and sitting. Subjects then performed a 12-week progressive, unilateral RT program of the nondominant arm with the dominant arm used as a comparison. Before and after RT, muscle strength was measured with the maximum voluntary contraction and one repetition maximum, while MRI measured muscle, fat, and bone volume. We will discuss the history of how FAMuSS originated, provide a brief overview of the FAMuSS methods, and summarize our major findings regarding genotype associations with muscle strength and size, body composition, cardiometabolic biomarkers, and physical activity.
    12/2013; 2013:643575. DOI:10.1155/2013/643575
  • Source
    • "Our main finding was that the variant R allele of the MSTN K153R polymorphism is associated with exceptional longevity in the two independent cohorts we studied, with a significantly higher proportion of this AGE (2013) 35:2445–2454 2449 Author's personal copy allele in the group of centenarians (cases) compared with their controls. In fact, the frequency of the R allele in our centenarians (7.1 % in Spaniards and 7.6 % in Italians) was approximately twofold higher than that previously reported in the literature for European Caucasians, i.e. 3–4 % (Corsi et al. 2002; Ferrell et al. 1999; Kostek et al. 2009). Despite the complexity of the ageing process and the fact that exceptional longevity is likely a polygenic trait with numerous candidate genes exerting an effect either individually or in complex interactions, single-gene mutations (like maybe the one we studied here) may suffice to delay the onset of age-related phenotypes in a variety of model organisms, from yeast to mammals (Bjedov and Partridge 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The myostatin (MSTN) gene is a candidate to influence extreme longevity owing to its role in modulating muscle mass and sarcopenia and especially in inhibiting the main nutrient-sensing pathway involved in longevity, i.e. mammalian target of rapamycin. We compared allele/genotype distributions of the exonic MSTN variants K153R (rs1805086), E164K (rs35781413), I225T and P198A, in Spanish centenarians (cases, n = 156; 132 women, age range 100-111 years) and younger adults (controls, n = 384; 167 women, age <50 years). No subject of either group carried a mutant allele of the E164K, I225T or P198A variation. The frequency of the variant R allele was significantly higher in centenarians (7.1 %) than in controls (2.7 %) (P = 0.001). The odds ratio of being a centenarian if the subject had the R allele was 3.48 (95 % confidence interval 1.67-7.28, P = 0.001), compared to the control group, after adjusting for sex. The results were replicated in an Italian cohort (centenarians, n = 79 (40 women), age range 100-104 years; younger controls, n = 316 (155 women), age <50 years), where a higher frequency of the R allele in centenarians (7.6 %) compared to controls (3.0 %) (P = 0.004) was independently confirmed. Although more research is needed, the variant allele of the MSTN K153R polymorphism could be among the genetic contributors associated with exceptional longevity.
    Age 01/2013; 35(6). DOI:10.1007/s11357-013-9513-3 · 3.45 Impact Factor
Show more