No association between ACTN3 R577X and ACE I/D polymorphisms and endurance running times in 698 Caucasian athletes

Papadimitriou, Ioannis; Lockey, Sarah J; Voisin, Sarah; Herbert, Adam J.; Garton, Fleur; Houweling, Peter J.; Cięszczyk, Paweł; Maciejewska-Skrendo, Agnieszka; Sawczuk, Marek; Massidda, Myosotis; Calò, Carla Maria; Astratenkova, Irina V.; Kouvatsi, Anastasia; Druzhevskaya, Anastasiya M.; Michaux, Jacques; Ahmetov, Ildus I.; Stebbings, Georgina K.; Heffernan, Shane M.; Day, Stephen H.; Erskine, Robert M.; Pedlar, Charles R.; Kipps, Courtney; North, Klaus; Williams, Alun G.; Eynon, Nir

doi:10.1186/s12864-017-4412-0

Cited by 60 publications

(52 citation statements)

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“…Using a large cohort (n = 346; 555 best personal times) of elite Caucasian athletes with reported running times we identified that ACTN3 577RR individuals had significantly faster running times over 200 m, compared to XX and that the ACTN3 genotype accounted for 0.92% of the difference in sprint speed (Papadimitriou et al, 2016a). However, when the same quantitative approach was used for long distance runners, we found no association between the ACTN3 XX genotype and endurance performance (Papadimitriou et al, 2018), a finding consistent with the majority of case-control studies (Table 2a and…”

Section: Case-control Studiesmentioning

confidence: 99%

Is evolutionary loss our gain? The role of ACTN3 p.Arg577Ter (R577X) genotype in athletic performance, ageing, and disease

et al. 2018

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A common null polymorphism in the ACTN3 gene (rs1815739:C>T) results in replacement of an arginine (R) with a premature stop codon (X) at amino acid 577 in the fast muscle protein α‐actinin‐3. The ACTN3 p.Arg577Ter allele (aka p.R577* or R577X) has undergone positive selection, with an increase in the X allele frequency as modern humans migrated out of Africa into the colder, less species‐rich Eurasian climates suggesting that the absence of α‐actinin‐3 may be beneficial in these conditions. Approximately 1.5 billion people worldwide are completely deficient in α‐actinin‐3. While the absence of α‐actinin‐3 influences skeletal muscle function and metabolism this does not result in overt muscle disease. α‐Actinin‐3 deficiency (ACTN3 XX genotype) is constantly underrepresented in sprint/power performance athletes. However, recent findings from our group and others suggest that the ACTN3 R577X genotype plays a role beyond athletic performance with effects observed in ageing, bone health, and inherited muscle disorders such as McArdle disease and Duchenne muscle dystrophy. In this review, we provide an update on the current knowledge regarding the influence of ACTN3 R577X on skeletal muscle function and its potential biological and clinical implications. We also outline future research directions to explore the role of α‐actinin‐3 in healthy and diseased populations.

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Section: Case-control Studiesmentioning

confidence: 99%

Is evolutionary loss our gain? The role of ACTN3 p.Arg577Ter (R577X) genotype in athletic performance, ageing, and disease

et al. 2018

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“…Although these findings in West European populations support the hypothesis that the iron-increasing HFE rs1799945 G allele is favorable for endurance performance, replication studies in different ethnic groups using different designs are warranted. This approach leads to the exclusion of false-positive genetic associations (Eynon et al 2013;Zarebska et al 2017;Papadimitriou et al 2018;Yvert et al 2018;Guilherme et al 2019;Pickering et al 2019).…”

Section: Introductionmentioning

confidence: 99%

The association of HFE gene H63D polymorphism with endurance athlete status and aerobic capacity: novel findings and a meta-analysis

et al. 2020

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Purpose Iron is an important component of the oxygen-binding proteins and may be critical to optimal athletic performance. Previous studies have suggested that the G allele of C/G rare variant (rs1799945), which causes H63D amino acid replacement, in the HFE is associated with elevated iron indexes and may give some advantage in endurance-oriented sports. The aim of the present study was to investigate the association between the HFE H63D polymorphism and elite endurance athlete status in Japanese and Russian populations, aerobic capacity and to perform a meta-analysis using current findings and three previous studies. Methods The study involved 315 international-level endurance athletes (255 Russian and 60 Japanese) and 809 healthy controls (405 Russian and 404 Japanese). Genotyping was performed using micro-array analysis or by PCR. VO 2max in 46 male Russian endurance athletes was determined using gas analysis system. Results The frequency of the iron-increasing CG/GG genotypes was significantly higher in Russian (38.0 vs 24.9%; OR 1.85, P = 0.0003) and Japanese (13.3 vs 5.0%; OR 2.95, P = 0.011) endurance athletes compared to ethnically matched controls. The meta-analysis using five cohorts (two French, Japanese, Spanish, and Russian; 586 athletes and 1416 controls) showed significant prevalence of the CG/GG genotypes in endurance athletes compared to controls (OR 1.96, 95% CI 1.58-2.45; P = 1.7 × 10-9). Furthermore, the HFE G allele was associated with high VȮ 2max in male athletes [CC: 61.8 (6.1), CG/GG: 66.3 (7.8) ml/min/kg; P = 0.036]. Conclusions We have shown that the HFE H63D polymorphism is strongly associated with elite endurance athlete status, regardless ethnicities and aerobic capacity in Russian athletes. Keywords Gene • Genotype • Hemochromatosis • Endurance performance • Athletes Abbreviations CI Confidence intervals DNA Deoxyribonucleic acid EDTA Ethylenediaminetetraacetic acid GWAS Genome-wide association studies HFE Homeostatic iron regulator (hemochromatosis gene) HH Hereditary hemochromatosis HWE Hardy-Weinberg equilibrium PCR Polymerase chain reaction RFLP Restriction fragment length polymorphism SNP Single-nucleotide polymorphism STREGA Strengthening the reporting of genetic association TFRC Transferrin receptor VȮ 2max Maximal oxygen consumption Communicated by Michael Lindinger.

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“…Alpha-actinin-3 has been associated with alterations of the contractile properties of the sarcomere in type II muscle fibers [16], effects on the differentiation of muscle fiber type or hypertrophy through indirect interactions between alpha-actinin-3 and signaling proteins such as calcineurin [37], alterations of the ability to resist and/or recover from muscle damage caused by exercise [27], changes to the metabolic profile of muscle fibers through altered interactions with metabolic enzymes [18], and improved glycogen consumption or signaling for muscle hypertrophy [25]. None of these scenarios is exclusive of any other, and the actual mechanism is likely to be a combination of several of these processes.…”

Section: Introductionmentioning

confidence: 99%

“…The genotype that does not express alpha-actinin-3 (ACTN3-XX) has been linked to activities with a predominance of aerobic endurance [1,4,5,13,35]. Nonetheless, a recent multi-cohort quantitative analysis demonstrated that it is unlikely that the ACTN3-XX genotype provides an advantage in competitive endurance running performance [27].…”

Section: Introductionmentioning

confidence: 99%

Evidence for a Role of ACTN3 R577X Polymorphism in Football Player’s Career Progression

et al. 2018

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The aim was to investigate a possible role of the ACTN3 R577X polymorphism in a Brazilian football player’s career progression. 2 questions were formulated: 1. Does ACTN3 polymorphism affect the probability of an individual being a professional football player? 2. Does this polymorphism affect the progression of the athlete throughout his career? The study included 353 players from first division Brazilian football clubs in the following categories: under-14 (U-14), U-15, U-17, U-20, and professional (PRO). The control group (CON) was composed of 100 healthy non-athletes. The chi-squared test was used to assess differences between the allele and genotype frequencies. Comparing football categories, the XX genotype was less frequent among professional players than in the U-20 (p<0.05) or the U-15 category (p<0.05). The RX genotype also presented more frequently in the PRO category than the U-14 category (p<0.05). Moreover, a trend towards a higher frequency of the RX genotype and a lower frequency of the XX genotype was observed in the professional category compared to U-20. These results suggest that the genotype in the ACTN3 polymorphism affects the probability of a football player progressing throughout his career and becoming professional, meaning that playing football selects against the ACTN3 XX genotype.

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No association between ACTN3 R577X and ACE I/D polymorphisms and endurance running times in 698 Caucasian athletes

Cited by 60 publications

References 38 publications

Is evolutionary loss our gain? The role of ACTN3 p.Arg577Ter (R577X) genotype in athletic performance, ageing, and disease

Is evolutionary loss our gain? The role of ACTN3 p.Arg577Ter (R577X) genotype in athletic performance, ageing, and disease

The association of HFE gene H63D polymorphism with endurance athlete status and aerobic capacity: novel findings and a meta-analysis

Evidence for a Role of ACTN3 R577X Polymorphism in Football Player’s Career Progression

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