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Angiotensin‐Converting Enzyme Genotype Affects the Response of Human Skeletal Muscle to Functional Overload
Open accessAbstract
The response to strength training varies widely between individuals and is considerably influenced by genetic variables, which until now, have remained unidentified. The deletion (D), rather than the insertion (I), variant of the human angiotensin‐converting enzyme (ACE) genotype is an important factor in the hypertrophic response of cardiac muscle to exercise and could also be involved in skeletal muscle hypertrophy – an important factor in the response to functional overload. Subjects were 33 healthy male volunteers with no experience of strength training. We examined the effect of ACE genotype upon changes in strength of quadriceps muscles in response to 9 weeks of specific strength training (isometric or dynamic). There was a significant interaction between ACE genotype and isometric training with greater strength gains shown by subjects with the D allele (mean ± S.E.M.: II, 9.0 ± 1.7%; ID, 17.6 ± 2.2%; DD, 14.9 ± 1.3%, ANOVA, P 0.05). A consistent genotype and training interaction (ID DD II) was observed across all of the strength measures, and both types of training. ACE genotype is the first genetic factor to be identified in the response of skeletal muscle to strength training. The association of the ACE I/D polymorphism with the responses of cardiac and skeletal muscle to functional overload indicates that they may share a common mechanism. These findings suggest a novel mechanism, involving the renin‐angiotensin system, in the response of skeletal muscle to functional overload and may have implications for the management of conditions such as muscle wasting disorders, prolonged bed rest, ageing and rehabilitation, where muscle weakness may limit function.
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“Erskine et al. (30), reported average isometric strength gains ~2-fold greater than we have found [31% vs. 11.5–18.2% (31, 32)]”
From What makes long-term resistance-trained individuals so strong? A comparison of skeletal muscle morphology, architecture, and joint mechanics (2020) · cites this paper as [32]
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“mechanism underlying the association of the D allele with power-oriented, anaerobic sports is most likely mediated through differences in skeletal muscle strength gain (14).”
BackgroundWilson, G. C., Mavros, Y., Tajouri, L., & Singh, M. F. (2019) · Journal of Aging and Physical Activity · doi:10.1123/japa.2018-0155 · Cited by 14
A Quantitative Trait Locus on 13q14.2 for Trunk Strength
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BackgroundCan genotype determine the sports phenotype? A paradigm shift in sports medicine
Ghosh, A., & Mahajan, P. B. (2016) · Journal of Basic and Clinical Physiology and Pharmacology · doi:10.1515/jbcpp-2015-0090 · Cited by 14
“It enhances the muscle strength gain [26, 27].”
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Self-citationGenomic biomarkers and clinical outcomes of physical activity
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Kuperus, E., van der Meijden, J. C., Groen, S. L. M. I. ‘., Kroos, M. A., Hoogeveen‐Westerveld, M., Rizopoulos, D., Martinez, M., Kruijshaar, M. E., van Doorn, P. A., van der Beek, N. A. M. E., et al. (2018) · PLoS ONE · doi:10.1371/journal.pone.0208854 · Cited by 12
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“Meanwhile, the ACE D-allele has been associated with increased muscle strength (13,14,18) and anaerobic performance (12).”
BackgroundYusof, H. A., & Muhamed, A. M. C. (2021) · Sport Sciences for Health · doi:10.1007/s11332-020-00712-9 · Cited by 11
Montgomery, H., & Dhamrait, S. S. (2002) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00875.2001 · Cited by 11
Self-citationChiu, Y., Lai, J., Tseng, C.-Y., et al. (2019) · Medicine · doi:10.1097/md.0000000000016476 · Cited by 10
“Physiologically, the ACE polymorphism is linked to difference in contraction profiles, muscle strength, and other muscle parameters in human studies.([8,22]) Left ventricular mass is also reported to be correlated with the ACE polymorphism, although there are many conflicting reports in subjects and patients under dif…”
BackgroundCorrà, U., Mezzani, A., Giannuzzi, P., & Tavazzi, L. (2002) · Progress in Cardiovascular Diseases · doi:10.1053/pcad.2002.127490 · Cited by 10
Lack of association of the ACE genotype with the muscle strength response to resistance training
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“Earlier, Folland et al. (2000) found that the knee extensor isometric strength gains was associated with ACE I/D genotype, with young men that carry the D-allele presenting greater strength increases than II homozygous after 9 weeks of RT. However the baseline results for 1RM and isokinetic strength were similar among…”
BackgroundResultInfluentialACE and ACTN3 genes polymorphisms among female Hungarian athletes in the aspect of sport disciplines
Bosnyák, E., Trájer, E., Udvardy, A., et al. (2015) · Acta Physiologica Hungarica · doi:10.1556/036.102.2015.4.12 · Cited by 9
“A significantly higher muscle strength increase was shown among the members possessing D allele (4).”
BackgroundEFFECT OF STRENGTH TRAINING ON AGING MUSCLES OF ELDERLY PEOPLE
Kuno, S., Murakami, H., Baba, S., Kim, J., & KAMIOKA, M. (2003) · 体力科學 · doi:10.7600/jspfsm1949.52.17 · Cited by 9
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Differential response to resistance training in CHF according to ACE genotype
Williams, A. D., Anderson, M. J., Selig, S., Carey, M., Febbraio, M. A., Hayes, A., Toia, D., Harrap, S. B., & Hare, D. L. (2010) · International Journal of Cardiology · doi:10.1016/j.ijcard.2010.02.012 · Cited by 8
“The potential synergistic actions of angiotensin II in combination with mechanical loading provides a mechanism by which the previously observed (16, 17) greater increases in strength following resistance training in subjects with the D allele may have occurred.”
BackgroundResultHeterogeneity of Physical Function Responses to Exercise in Older Adults
Nicklas, B. J. (2010) · Perspectives on Psychological Science · doi:10.1177/1745691610383512 · Cited by 8
“Two published intervention studies in young adults show disparate findings regarding the effects of strength training on muscle size and strength gains (Folland et al., 2000; Pescatello et al., 2007).”
BackgroundHamstring injury prevention: A role for genetic information?
Pickering, C., & Kiely, J. (2018) · Medical Hypotheses · doi:10.1016/j.mehy.2018.07.011 · Cited by 3
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“104 107 The PPARG gene is involved with rs1801282 SNP ( PPARG Pro12Ala) in the modulation of muscle modi-fications associated with exercise.”
Personal Genetics – Sports Utility Vehicle?
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“The I variant appears to confer endurance performance (76), the D variant appears to be associated with muscle growth and confers an advantage in power sports (77).”
BackgroundAngiotensin-converting enzyme and human physical performance
Payne, J., & Montgomery, H. (2004) · Equine and comparative exercise physiology · doi:10.1079/ecp200432 · Cited by 7
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“In addition, ACE genotypes in adults, were associated with strength response to muscle training and D-allele carriers experience greater strength increase than II homozygotes [9,23].”
BackgroundResultGenetics and Sprint, Strength, and Power Performance
Jacques, M., Eynon, N., & Hanson, E. D. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-813922-6.00031-x · Cited by 6
Genetic Variation and Physical Performance
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“Several studies identified an association between the presence of a specific allele of the gene encoding the angiotensin-converting enzyme (ACE) and an individual’s endurance or strength capacity (Gayagay et al., 1998; Folland et al., 2000; Woods et al., 2000; Williams et al., 2004).”
BackgroundTalent selection and genetics in sport
ÖZVEREN, Y., Özçaldıran, B., Durmaz, B., et al. (2014) · DergiPark (Istanbul University) · doi:10.15314/tjse.54245 · Cited by 4
“lean body messes with exercise (37, 38) and a greater muscular strength develops as a result of resistance trainings (11, 15).”
BackgroundMusculoskeletal Tissue Injury and Repair
Gharaibeh, B., Deasy, B. M., Lavasani, M., Cummins, J. H., Li, Y., & Huard, J. (2012) · Elsevier eBooks · doi:10.1016/b978-0-12-381510-1.00062-4 · Cited by 4
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“However, several studies involving small cohorts of participants (n\ 60) reported lack of significant difference between ACE gene ID polymorphism and muscular strength [75, 80, 81].”
BackgroundGenetic Aspects of Muscular Strength and Size
Hubal, M. J., Urso, M. L., & Clarkson, P. M. (2011) · Humana Press eBooks · doi:10.1007/978-1-60761-355-8_7 · Cited by 4
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“In many studies, the insertion (I) allele has been associated with anabolic response to training and elite endurance performance, whilst the deletion (D) allele was associated with sprint or power performance [8–12], and both variants have been associated with response to strength training [13,14].”
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“Conversely, greater production of ANG II, which is a growth factor necessary for the hypertrophy of skeletal muscle, in the D allele carrier may confer an advantage for the short duration and high intensity activity that characterizes strength/power-oriented sports performance [14, 28].”
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Self-citationDay, S. H., Williams, C. A., Folland, J. P., et al. (2004) · European Journal of Applied Physiology · doi:10.1007/s00421-004-1078-5 · Cited by 4
“The D variant, where the 287-bp fragment is absent, appears to favour strength and power performance (Myerson et al. 1999; Folland et al. 2000; Woods et al. 2001).”
BackgroundSelf-citationACE gene, physical activity, and physical fitness
Williams, A. G., Day, S. H., & Dhamrait, S. S. (2002) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00540.2002 · Cited by 3
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“Conversely, an excess of the D allele has been reported among elite power-oriented athletes [27] in a mechanism that is most likely mediated by differences in skeletal muscle strength gain [17].”
BackgroundGenetic Roles in Muscle Strength
Kostek, M. C., Hubal, M. J., & Pescatello, L. S. (2007) · ACSMʼs Health & Fitness Journal · doi:10.1249/01.fit.0000262475.20949.bc · Cited by 2
“ACE I/D has been widely studied in a variety of athletes (12–14) and is linked to endurance capacity, response to endurance training, and muscle strength (15).”
BackgroundThe polymorphic ACE gene and resulting genotypes and allele frequencies within specific groups
Kranes, S. J., Gove, T. G., Dodson, K., et al. (2016) · SUNY Digital Repository Support (State University of New York System) · Cited by 2
Kurtuluş, M., Günay, M., Çetin, E., et al. (2018) · Gaziantep Üniversitesi Spor Bilimleri Dergisi · doi:10.31680/gaunjss.476196 · Cited by 2
Opening Up Possibilities Through Genomics
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Toshboltaeva, S. S., & Murtazina, E. P. (2011) · Bulletin of Experimental Biology and Medicine · doi:10.1007/s10517-011-1189-z · Cited by 1
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“However, it is worth noting that previous studies such as de Souza et al. (2013), Folland et al. (2000), Santana et al. (2011), and Williams et al. (2011) have found positive ACE results/associations with sample sizes smaller than in the present study (range n = 27 to n = 41).”
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Rebuttal from Prof. Le Gallais
(2007) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00338.2007b · Cited by 1
Genetic Aspects of Sprint, Strength and Power Performance
Hanson, E. D., & Eynon, N. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-396454-0.00029-1 · Cited by 1
Genetic Variation and Skeletal Muscle Traits: Implications for Sarcopenia
Roth, S. M. (2010) · Springer eBooks · doi:10.1007/978-90-481-9713-2_11 · Cited by 1
Genetic Variation of I/D Enzyme Converting Angiotensin (ACE) with Athlete Muscle Resistance
Hadi, I., & Rosyanti, L. (2019) · Health Notions · doi:10.33846/hn30306 · Cited by 1
“These findings illustrate a new mechanism, which involves the renin-angiotensin system((2)), so that it is important to understand the role of the ACE gene with physical performance and how this gene can change the subject's ability to respond to exercise but can have important implications in designing studies to tes…”
BackgroundKurtuluş, M., Günay, M., Çelenk, Ç., Cicioğlu, İ., & Kesici, T. (2019) · Ankara Üniversitesi Beden Eğitimi ve Spor Yüksekokulu SPORMETRE Beden Eğitimi ve Spor Bilimleri Dergisi · doi:10.33689/spormetre.641112 · Cited by 2
Genetic Markers in Social Science Research: Opportunities and Pitfalls
Vogler, G. P., & McClearn, G. E. (2008)
Genetic studies of elite athlete status
Wang, G. (2013) · Enlighten: Theses (The University of Glasgow) · doi:10.5525/gla.thesis.4597
Medicina personalizada en práctica deportiva
García, I. I. (2010) · Elsevier eBooks · doi:10.1016/b978-84-458-2025-4.00011-5
New Advances in Molecular Therapy for Muscle Repair after Diseases and Injuries
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Cycling Performance Following Intermittent Hypoxic Training using an Hypoxicator
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“1997; Folland et al., 2000). However, Folland et al. (2000) related these findings to the notion that the D allele may regulate hypertrophic responses in skeletal muscle.”
BackgroundResultInfluentialReview of genetic research and testing in sport
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ANGIOTENSIN I CONVERTING ENZYME GENE INSERTION/DELETION POLYMORPHISM AND HUMAN PHYSICAL PERFORMANCE
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تنوع الاشكال الجيني لـ (ACE) وعلاقته ببعض القدرات البدنية للرماة بالمسدس الهوائي
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Metadata
- Authors
- Folland, J., Leach, B., Little, T., Hawker, K., Myerson, S., Montgomery, H., & Jones, D.
- Affiliations
- University College London (GB)
- Corresponding author
- Folland, Jonathan
- Venue
- Experimental Physiology
- Publisher
- Wiley
- Published
- 2000-09
- Volume
- 85
- Issue
- 5
- Pages
- 575-579
- ISSN
- 0958-0670 (ISSN-L)
- 1469-445X
- OpenAlex
- W2152660257
- Cited by
- 208
- References
- 0
- Citations by year
- 2026: 1 · 2025: 3 · 2023: 1 · 2022: 1 · 2021: 5 · 2020: 6 · 2019: 6 · 2018: 9 · 2017: 5 · 2016: 8 · 2015: 7 · 2014: 6 · 2013: 16 · 2012: 17
- FWCI
- 3.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Experimental Physiology (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Physical Performance
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Physiology (medical) › Cardiovascular and exercise physiology
- Keywords
- angiotensin-converting enzyme, ACE I/D polymorphism, skeletal muscle hypertrophy, resistance training, functional overload, quadriceps strength, isometric training, dynamic training, renin-angiotensin system, muscle atrophy
- MeSH terms
- Adolescent, Adult, Alleles, Genotype, Humans, Hypertrophy, Isoenzymes, Isometric Contraction, Peptidyl-Dipeptidase A, Male, Physical Fitness, Polymorphism, Genetic, Exercise, Polymerase Chain Reaction, Weight-Bearing, Muscle, Skeletal
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