AGTR2 gene polymorphism is associated with muscle fibre composition, athletic status and aerobic performance

Abstract

New Findings r What is the central question of this study?Variations in genes are considered to be molecular determinants maintaining the expression of the slow or fast myosin heavy chains of adult skeletal muscle. The role of polymorphisms of candidate genes involved in skeletal muscle development, energy homeostasis and thyroid and calcium metabolism in the determination of muscle fibre type has not previously been reported. r What is the main finding and its importance?We show that the AGTR2 rs11091046 C allele is associated with an increased proportion of slow-twitch muscle fibres, endurance athlete status and aerobic performance. Such findings have important implications for our understanding of muscle function in both health and disease.Muscle fibre type is a heritable trait and can partly predict athletic success. It has been proposed that polymorphisms of genes involved in the regulation of muscle fibre characteristics may predispose the muscle precursor cells of a given individual to be predominantly fast or slow. In the present study, we examined the association between 15 candidate gene polymorphisms and muscle fibre type composition of the vastus lateralis muscle in 55 physically active, healthy men. We found that rs11091046 C allele carriers of the angiotensin II type 2 receptor gene (AGTR2; involved in skeletal muscle development, metabolism and circulatory homeostasis) had a significantly higher percentage of slow-twitch fibres than A allele carriers [54.2 (11.1) versus 45.2 (10.2)%; P = 0.003]. These data indicate that 15.2% of the variation in muscle fibre composition of the vastus lateralis muscle can be explained by the AGTR2 genotype. Next, we investigated the frequencies of the AGTR2 alleles in 2178 Caucasian athletes and 1220 control subjects. The frequency of the AGTR2 C allele was significantly higher in male and female endurance athletes compared with power athletes (males, 62.7 versus 51.7%, P = 0.0038; females, 56.6 versus 48.1%, P = 0.0169) and control subjects (males, 62.7 versus 51.0%, P = 0.0006; elite female athletes, 65.1 versus 55.2%, P = 0.0488). Furthermore, the frequency of the AGTR2 A allele was significantly over-represented in female power athletes (51.9%) in comparison to control subjects (44.8%, P = 0.0069). We also found that relative maximal oxygen consumption was significantly greater in male endurance athletes with the AGTR2 C allele compared with AGTR2 A allele carriers [n = 28; 62.3 (4.4) versus 57.4 (6.0) ml min −1 kg −1 ; P = 0.0197]. Taken together, these results demonstrate that the AGTR2 gene C allele is associated with an increased proportion of slow-twitch muscle fibres, endurance athlete status and aerobic performance, while the A allele is associated with a higher percentage of fast-twitch fibres and power-oriented disciplines.

Heritability estimates of muscle strength‐related phenotypes: A systematic review and meta‐analysis

“…Alphaactinin-3 gene (ACTN3), peroxisome proliferator-activated receptor alpha gene, angiotensin II type 2 receptor gene, and angiotensin-converting enzyme gene polymorphisms have been reported to be associated with muscle fiber composition. [50][51][52][53] Moreover, polymorphisms in ACTN3, the product of which is a major component of Z-disks in fast-twitch muscle fibers 9 and the myostatin gene, the product of which suppress muscle growth, 54 explained the individual differences in muscle strength-related phenotypes. However, it remains unclear to what extent over 20 polymorphisms that have been reported to be related to muscle strength [55][56][57] explain the H 2 -msp.…”

Current Progress in Sports Genomics

“…The C3123A (also known as rs11091046 or C4599A) polymorphism of the AGTR2 gene located within the 3-UTR of exon 3 has been reported to be associated with several cardiovascular phenotypes. By studying 2178 athletes from Russia and Poland, Mustafina et al [4] found that rs11091046 C allele carriers of the AGTR2 gene had a significantly higher percentage of slow-twitch fibers than A allele carriers [54.2 (11.1)% vs. 45.2 (10.2)%; P ¼ 0.003] in the group of 55 physically active, healthy men. The frequency of the AGTR2 C allele was significantly higher in male and female endurance athletes compared with power athletes (males: 62.7% vs. 51.7%; P ¼ 0.0038; females: 56.6% vs. 48.1%; P ¼ 0.0169) and control subjects (males: 62.7% vs. 51.0%; P ¼ 0.0006; elite female athletes: 65.1% vs. 55.2%; P ¼ 0.0488).…”

“…Cross-sectional association studies are another type of study design in sports genomics and examine whether athletes with one genotype (or allele) of a particular DNA sequence show different measures of a trait (e.g., VO 2max , strength measures, percentage of fast-twitch muscle fibers, cardiac size, lactate, etc.) compared to the rest of the sample [4].…”

Sports Medicine - Open

“…Additionally, studies have been performed primarily in healthy adults (physically active college students, moderately trained and recreationally active subjects) and not high-level athletes; although not universally confirmed, athletes with more extensive training backgrounds may have distinct phenotypes [79-81] and genotypes than normally active subjects [82]. Moreover, to the authors’ best knowledge, there is no research concerning how the distinct genotypes that can be found within a high-level group of athletes [82-84] may influence the individual responses to concurrent training.…”