The ACE Gene and Human Performance

Abstract

Some 12 years ago, a polymorphism of the angiotensin I-converting enzyme (ACE) gene became the first genetic element shown to impact substantially on human physical performance. The renin-angiotensin system (RAS) exists not just as an endocrine regulator, but also within local tissue and cells, where it serves a variety of functions. Functional genetic polymorphic variants have been identified for most components of RAS, of which the best known and studied is a polymorphism of the ACE gene. The ACE insertion/deletion (I/D) polymorphism has been associated with improvements in performance and exercise duration in a variety of populations. The I allele has been consistently demonstrated to be associated with endurance-orientated events, notably, in triathlons. Meanwhile, the D allele is associated with strength- and power-orientated performance, and has been found in significant excess among elite swimmers. Exceptions to these associations do exist, and are discussed. In theory, associations with ACE genotype may be due to functional variants in nearby loci, and/or related genetic polymorphism such as the angiotensin receptor, growth hormone and bradykinin genes. Studies of growth hormone gene variants have not shown significant associations with performance in studies involving both triathletes and military recruits. The angiotensin type-1 receptor has two functional polymorphisms that have not been shown to be associated with performance, although studies of hypoxic ascent have yielded conflicting results. ACE genotype influences bradykinin levels, and a common gene variant in the bradykinin 2 receptor exists. The high kinin activity haplotye has been associated with increased endurance performance at an Olympic level, and similar results of metabolic efficiency have been demonstrated in triathletes. Whilst the ACE genotype is associated with overall performance ability, at a single organ level, the ACE genotype and related polymorphism have significant associations. In cardiac muscle, ACE genotype has associations with left ventricular mass changes in response to stimulus, in both the health and diseased states. The D allele is associated with an exaggerated response to training, and the I allele with the lowest cardiac growth response. In light of the I-allele association with endurance performance, it seems likely that other regulatory mechanisms exist. Similarly in skeletal muscle, the D allele is associated with greater strength gains in response to training, in both healthy individuals and chronic disease states. As in overall performance, those genetic polymorphisms related to the ACE genotype, such as the bradykinin 2 gene, also influence skeletal muscle strength. Finally, the ACE genotype may influence metabolic efficiency, and elite mountaineers have demonstrated an excess of I alleles and I/I genotype frequency in comparison to controls. Interestingly, this was not seen in amateur climbers. Corroboratory evidence exists among high-altitude settlements in both South America and India, where the I allele...

ACE I/D and ACTN3 R/X polymorphisms as potential factors in modulating exercise-related phenotypes in older women in response to a muscle power training stimuli

“…ACE has a key role in the endocrine rennin-angiotensin system (RAS), being responsible for catalyzing the conversion of angiotensin I into angiotensin II (Costa et al 2009). A few studies, however, have linked the potential importance of the RAS and ACE gene to skeletal muscle hypertrophy, a key determinant mechanism of strength and power enhancement in response to overload in healthy older men and women (Charbonneau et al 2008;Gordon et al 2001;Wagner et al 2006;Puthucheary et al 2011a). Historically, research has centered on an insertion-deletion (I/D-allele) polymorphism in intron 16, which is characterized by the presence (I-allele) or absence (D-allele) of a 287-bp Alu repeat sequence (Rieder et al 1999).…”

Genetic influence on exercise-induced changes in physical function among mobility-limited older adults

“…As such, the mode of exercise appears to be an important factor in determining the influence of the I/D polymorphism on adaptations to training. Accordingly, although the data are not entirely consistent, longitudinal intervention studies and cross-sectional studies from young athletes have predominantly reported that individuals homozygous for the I allele (II) display strong responses to aerobic training while the DD genotype is associated with better responsiveness to resistance training (45,48). In summary, the ACE I/D polymorphism appears to modulate exercise responsiveness in young adults in a manner that is dependent on the mode of exercise performed.…”

Athletic Performance and Angiotensin I-Converting Enzyme Gene: Review

“…Endotel hücrelerinde membrana bağlı olarak bulunan ADE'nin AI'in, AII'ye dönüşümünü ve bradikininin parçalanmasını sağladığı ve böy-lece de dolaşımdaki homeostazda önemli rol oynadığı saptanmıştır. 25 ADE genindeki I/D polimorfizmi en çok araş-tırılan polimorfizmdir.…”

“…Yapılan çalışmalar, elit sporcularda yüksek performansın sadece genetik özellik-lerden kaynaklanmadığını, aynı zamanda antrenman ve beslenme gibi uygun çevresel koşulların bir araya gelmesi sonucu oluştuğunu göstermektedir. 25,57 Genetik faktörlerin, sporcu performansındaki deği-şimlerini anlayabilmek için hem genetik hem de çevresel etkenlerin ayrı ayrı ele alınması gerekmektedir. Ayrıca, genetik ile çevresel faktörler arasındaki korelasyonun incelenmesi de önemlidir.…”