Thomas Yvert

Is there an association between ACTN3 R577X polymorphism and muscle power phenotypes in young, non‐athletic adults?

We investigated the association between ACTN3 R577X polymorphism and jumping (vertical squat and counter‐movement jump tests) and sprint ability (30 m dash) in non‐athletic, healthy young adults [N=284 (217 male), mean (SD) age: 21 (2) years]. We analyzed the differences in the study phenotypes among ACTN3 R577X genotypes by one‐way analysis of covariance before and after adjusting for sex, age, weight and height (confounders). We also compared the genotype and allele frequencies between those with the best and worst results in the aforementioned tests (≥90th vs <90th of the sex‐specific percentile, respectively). We used logistic regression to calculate the odds ratio (OR) for having the best performance. We did not observe a significant association between ACTN3 R577X genotypes and the study phenotypes before and after adjusting for potential confounders, nor after analyzing males and females separately. We did not observe significant differences in genotype frequencies between those with the best or the worst performance. The OR for an individual with the RR genotype to be in the top 10 percentile was <1.00 for jump tests and <1.015 for sprint tests (all P>0.05). In summary, α‐actinin‐3 deficiency does not negatively influence the ability to generate explosive leg muscle power in a young non‐athletic population.

ACTN3 R577X Polymorphism does not Influence Explosive Leg Muscle Power in Elite Volleyball Players

We examined the association of R577X polymorphism (rs1815739) in the α‐actinin‐3 (ACTN3) gene with “explosive” leg muscle power performance in a group of male and female elite volleyball players (n=66, 31 men, 35 women) and in a group of non‐athletic male and female young adults (n=334, 243 men, 91 women). We assessed power performance by means of the vertical squat and counter‐movement jump tests. We also determined whether the genotypic frequencies of the ACTN3 R577X genotypes differed between groups. We did not observe any effect of the ACTN3 R577X polymorphism on study phenotypes in both groups, regardless of gender (all P>0.05). Genotype frequencies were similar between volleyball and control groups (P=0.095). Moreover, we did not find an association between the ACTN3 R577X polymorphism and the likelihood of being an elite volleyball player using the dominant (RR vs RX+XX) and the recessive model (RR+RX vs XX). In summary, these findings suggest that the ACTN3 R577X polymorphism does not influence explosive leg muscle power in elite volleyball players.

ACE and ACTN3 Genes and Muscle Phenotypes in Nonagenarians

We studied the association of ACE and ACTN3 polymorphisms with skeletal muscle phenotypes (i. e. upper and lower body muscular strength and functional tests) in Spanish nonagenarian subjects [n=41, 33 women, 8 men, age: 90-97 years]. Mean values of the study phenotypes were not significantly different (all P>0.05) between ACE and ACTN3 genotypes. The analyses of the combined effects between genotypes ( ACE DD & ACTN3 RR/RX vs. ACE II/ID & ACTN3 XX) did not yield any significant difference. Our data suggest that, in the elderly, the influence of genetic factors on muscle phenotype traits is not reducible to a few single polymorphisms, including ACE and ACTN3 variants.

ApoE gene and exceptional longevity: Insights from three independent cohorts

The ApoE gene is associated with the risk of Alzheimer or cardiovascular disease but its influence on exceptional longevity (EL) is uncertain. Our primary purpose was to determine, using a case-control design, if the ApoE gene is associated with EL. We compared ApoE allele/genotype frequencies among the following cohorts: cases (centenarians, most with 1+ major disease condition; n=163, 100-111years) and healthy controls (n=1039, 20-85years) from Spain; disease-free cases (centenarians; n=79, 100-104years) and healthy controls (n=597, age 27-81years) from Italy; and cases (centenarians and semi-supercentenarians, most with 1+ major disease condition; n=729, 100-116years) and healthy controls (n=498, 23-59years) from Japan. Our main findings were twofold. First, the ε4-allele was negatively associated with EL in the three cohorts, with the following odds ratio (OR) values (adjusted by sex) having been found: 0.55 (95% confidence interval (CI): 0.33, 0.94), P=0.030 (Spain); 0.41 (95%CI: 0.18, 0.99), P=0.05 (Italy); and 0.35 (95%CI: 0.26, 0.57), P<0.001 (Japan). Second, although no association was found in the Spanish cohort (OR=1.42 (95%CI: 0.89, 2.26), P=0.145), the ε2-allele was positively associated with EL in the Italian (OR=2.14 (95%CI: 1.18, 3.45), P=0.01) and Japanese subjects (OR=1.81 (95%CI: 1.25, 2.63), P=0.002). Notwithstanding the limitations of case-control designs, our data suggest that the ApoE might be a candidate to influence EL. The ε4-allele appears to decrease the likelihood of reaching EL among individuals of different ethnic/geographic origins. An additional, novel finding of our study was that the ε2-allele might favor EL, at least in the Italian and Japanese cohorts.

The C allele of the AGT Met235Thr polymorphism is associated with power sports performance

Whether the Met235Thr (rs699) variation in the angiotensinogen (AGT) gene, encoding a threonine instead of a methionine in codon 235 of the mature protein, is associated with athletic performance remains to be elucidated. We compared the genotype and allele frequencies for the AGT Met235Thr variation (rs699) in 119 nonathletic controls, 100 world-class endurance athletes (professional cyclists, Olympic-class runners), and 63 power athletes (top-level jumpers, throwers, sprinters). Participants were all males and from the same descent (Caucasian) for > or =3 generations. The proportion of the CC genotype was significantly higher in the power group (34.9%) than in either the control (16%) or the endurance group (16%) (p = 0.008 and p = 0.005, respectively). The odds ratio (95% CI) of being a power athlete if the subject has a CC genotype was 1.681 (1.176-2.401), compared with the control group. In summary, the C allele of the AGT Met235Thr polymorphism might favour power sports performance. Although more research is needed, this could be attributed to the higher activity of angiotensin II, a skeletal muscle growth factor.

The K153R Polymorphism in the Myostatin Gene and Muscle Power Phenotypes in Young, Non-Athletic Men

The Lys(K)153Arg(R) polymorphism in exon 2 (rs1805086, 2379 A>G replacement) of the myostatin (MSTN) gene is a candidate to influence skeletal muscle phenotypes. We examined the association between the MSTN K153R polymorphism and ‘explosive’ leg power, assessed during sprint (30 m) and stationary jumping tests [squat (SJ) and counter-movement jumps (CMJ)] in non-athletic young adults (University students) [n = 281 (214 men); age: 21–32 years]. We also genotyped the MSTN exonic variants E164K (rs35781413), I225T, and P198A, yet no subject carried any of these variant MSTN alleles. As for the K153R polymorphism, we found only one woman with the KR genotype; thus, we presented the results only for men. The results of a one-way ANCOVA (with age, weight and height entered as covariates) showed that men with the KR genotype (n = 15) had a worse performance in vertical jumps compared with those with the KK genotype [SJ: vertical displacement of center of gravity (CG) of 35.17±1.42 vs. 39.06±0.39 cm, respectively, P = 0.009; CMJ: vertical displacement of CG of 36.44±1.50 vs. 40.63±0.41 cm, respectively, P = 0.008]. The results persisted after adjusting for multiple comparisons according to Bonferroni. Performance in 30 m sprint tests did however not differ by K153R genotypes. In summary, the MSTN K153R polymorphism is associated with the ability to produce ‘peak’ power during muscle contractions, as assessed with vertical jump tests, in young non-athletic men. Although more research is still needed, this genetic variation is among the numerous candidates to explain, alone or in combination with other polymorphisms, individual variations in muscle phenotypes.

Physical Inactivity and Low Fitness Deserve More Attention to Alter Cancer Risk and Prognosis

Sedentary lifestyle is associated with elevated cancer risk whereas regular physical activity (PA) and high cardiorespiratory fitness (CRF) have the opposite effect, with several biologic mechanisms mediating such associations. There is a need for lifestyle interventions aimed at increasing the PA levels and CRF of the general population and particularly cancer survivors. Furthermore, provocative data suggest a dose-dependent benefit of increasing levels of PA and/or CRF against cancer risk or mortality. Thus, current PA guidelines (≥150 min/wk of moderate-to-vigorous PA) may not be sufficiently rigorous for preventing cancer nor for extending cancer survivorship. Research targeting this issue is urgently needed. Promoting regular PA along with monitoring indicators of CRF and adiposity may provide powerful strategies to prevent cancer in populations, help patients with cancer more effectively deal with their disease and enhance secondary prevention programs in those who are affected by cancer. Cancer Prev Res; 8(2); 105–10. ©2014 AACR.

Are 'endurance' alleles 'survival' alleles? Insights from the ACTN3 R577X polymorphism.

Exercise phenotypes have played a key role for ensuring survival over human evolution. We speculated that some genetic variants that influence exercise phenotypes could be associated with exceptional survival (i.e. reaching ≥100years of age). Owing to its effects on muscle structure/function, a potential candidate is the Arg(R)577Ter(X) polymorphism (rs1815739) in ACTN3, the structural gene encoding the skeletal muscle protein α-actinin-3. We compared the ACTN3 R577X genotype/allele frequencies between the following groups of ethnically-matched (Spanish) individuals: centenarians (cases, n = 64; 57 female; age range: 100–108 years), young healthy controls (n = 283, 67 females, 216 males; 21±2 years), and humans who are at the two end-points of exercise capacity phenotypes, i.e. muscle endurance (50 male professional road cyclists) and muscle power (63 male jumpers/sprinters). Although there were no differences in genotype/allele frequencies between centenarians (RR:28.8%; RX:47.5%; XX:23.7%), and controls (RR:31.8%; RX:49.8%; XX:18.4%) or endurance athletes (RR:28.0%; RX:46%; XX:26.0%), we observed a significantly higher frequency of the X allele (P = 0.019) and XX genotype (P = 0.011) in centenarians compared with power athletes (RR:47.6%; RX:36.5%;XX:15.9%). Notably, the frequency of the null XX (α-actinin-3 deficient) genotype in centenarians was the highest ever reported in non-athletic Caucasian populations. In conclusion, despite there were no significant differences with the younger, control population, overall the ACTN3 genotype of centenarians resembles that of world-class elite endurance athletes and differs from that of elite power athletes. Our preliminary data would suggest a certain ‘survival’ advantage brought about by α-actinin-3 deficiency and the ‘endurance’/oxidative muscle phenotype that is commonly associated with this condition.

ACTN3 R577X Polymorphism and Explosive Leg-Muscle Power in Elite Basketball Players

PURPOSE To determine the association of the ACTN3 R577X polymorphism with leg-muscle explosive power in Spanish (white) elite basketball players and controls. PARTICIPANTS 100 (60 men) elite basketball players (cases) and 283 nonathletic controls. METHODS The authors assessed power performance by means of the vertical-squat and countermovement-jump tests. RESULTS Genotype distributions did not differ between groups (cases: 37.0% [RR], 42.0% [RX], and 21.0% [XX]; controls: 31.8% [RR], 49.8% [RX], and 18.4% [XX]; P = .353). The authors did not observe any effect of the ACTN3 R577X polymorphism on study phenotypes in either group, including when they performed the analyses separately in men and women. They found no association between the ACTN3 R577X polymorphism and the likelihood of being an elite basketball player using the dominant or the recessive model, and the results remained unaltered when the analyses were adjusted for sex, weight, height, and age or when performed for men and women separately. CONCLUSIONS Although the ACTN3 R577X is associated with explosive muscle performance and this phenotype is important in the sport of basketball (ie, during jumps), the authors found no association with leg explosive power in elite basket players or with the status of being this type of athlete.

Are Calcineurin Genes Associated with Athletic Status? A Function, Replication Study

PURPOSE Polymorphisms in calcineurin genes are candidates to explain individual variations in endurance sports performance owing to the pivotal role that the calcineurin signaling pathway plays in the regulation of important cardiac and skeletal muscle phenotypes. METHODS We compared genotypic/allelic frequencies in 55 single nucleotide polymorphisms (SNP) of the five genes (PPP3CA, PPP3CB, PPP3CC, PPP3R1, and PPP3R2) encoding the calcineurin protein subunits between 123 elite runners (cases, n = 61 women) and 125 healthy nonathletes (controls, n = 56 women) from the same ethnic background (Han Chinese) and used the dual-luciferase reporter assay to analyze the functional significance of the associated SNP. RESULTS The C allele of the PPP3CA rs3804358 polymorphism was overrepresented in athletes (17%) compared with controls (8%) (P = 0.003), whereas the T allele of the PPP3CB rs3763679 polymorphism was underrepresented in athletes (23%) compared with controls (37%) (P = 0.001). The luciferase reporter constructs containing C allele of the rs3804358 and rs3763679 polymorphisms produced significantly greater luciferase activity than that of the G or T alleles, respectively. However, the results on the two aforementioned polymorphisms were not corroborated in a Caucasian (Spanish) cohort of male elite endurance athletes (n = 100) and nonathletic male controls (n = 175). CONCLUSIONS Although there are large differences between ethnicities and more research is needed, our findings suggest that intronic polymorphisms of the calcineurin genes have functional significance and show evidence of association with elite endurance performance in the northern Han Chinese population.