Félix Gómez-Gallego

Is there an optimum endurance polygenic profile

We analysed seven genetic polymorphisms that are candidates to explain individual variations in human endurance phenotypic traits, at least in Caucasian people (ACE Ins/Del, ACTN3 Arg577Ter, AMPD1 Gln12Ter, CKMM 1170 bp/985 + 185 bp, HFE His63Asp, GDF‐8 Lys153Arg and PPARGC1A Gly482Ser) in 46 world‐class endurance athletes and 123 controls (all Spanish Caucasians). Using the model developed by Williams & Folland we determined (1) the ‘total genotype score’ (TGS, from the accumulated combination of the seven polymorphisms, with a maximum value of ‘100’ for the theoretically optimal polygenic score) in the non‐athlete (control) group, in the athlete group and in the total Spanish population, and (2) the probability for the occurrence of Spanish individuals with the ‘perfect’ polygenic endurance profile (i.e. TGS = 100). The probability of a Spanish individual possessing a theoretically optimal polygenic profile for up to the seven candidate genetic polymorphisms we studied was very small, i.e. ∼0.07% (or 1 in 1351 Spanish individuals). The mean TGS was higher in athletes (70.22 ± 15.58) than in controls (62.43 ± 11.45) and also higher than predicted for the total Spanish population (60.80 ± 12.1), suggesting an overall more ‘favourable’ polygenic profile in the athlete group. However, only three of the best Spanish endurance athletes (who are also amongst the best in the world) had the best possible score for up to six genes and none of them had the optimal profile. Other polymorphisms yet undiscovered as well as several factors independent of genetic endowment may explain why some individuals reach the upper end of the endurance performance continuum.

ACTN3 genotype in professional soccer players

The authors studied the frequency distribution of α-actinin-3 (ACTN3) R577X genotypes in 60 top-level professional soccer players. The results were compared with those of 52 elite endurance athletes and 123 sedentary controls. The per cent distribution of RR and RX genotypes in soccer players (48.3% and 36.7%) was significantly higher and lower, respectively, than controls (28.5% and 53.7%) and endurance athletes (26.5% and 52%) (p = 0.041). Although there are notable exceptions, elite soccer players tend to have the sprint/power ACTN3 genotype.

Mobilisation of mesenchymal cells into blood in response to skeletal muscle injury

Mesenchymal cells recruited to damaged tissues must circulate through the bloodstream. The absolute numbers of circulating mesenchymal stem cells (cMSCs) in two different models of acute and chronic skeletal muscle injury were determined. cMSCs were present in significantly higher numbers in both models than in healthy controls. These results support the hypothesis that MSCs are mobilised into the bloodstream after skeletal muscle tissue damage. These two models (acute and chronic) would be of value in the search for molecular mediators of mobilisation of MSCs into the circulation.

World-class performance in lightweight rowing: is it genetically influenced? A comparison with cyclists, runners and non-athletes

In this study, genotype frequencies of several polymorphisms that are candidates to influence sports performance (ie, ACTN3 R577X, ACE ID, PPARGC1A Gly482Ser, AMPD1 C34T, CKMM 985bp/1170bp and GDF8 (myostatin) K153R) were compared in 123 nonathletic controls, 50 professional cyclists, 52 Olympicclass runners and 39 world-class rowers (medallists in world championships, lightweight category). Significant differences in genotype distributions among the groups were not found except for the ACE gene, that is, lower (p<0.05) proportion of II in rowers (10.3%) than in the total subject population (22.3%). In summary, sports performance is likely polygenic with the combined effect of hundreds of genetic variants, one possibly being the ACE ID polymorphism (at least in the sports studied here), but many others remain to be identified.

Does the polygenic profile determine the potential for becoming a world-class athlete? Insights from the sport of rowing

We determined whether the polygenic profile computed with seven candidate polymorphisms (i.e., ACE, ACTN3, AMPD1, CKMM, HFE, GDF‐8 and PPARGC1A) for endurance performance is different in 39 world‐class and 15 national‐class Spanish (Caucasian) lightweight rowers. The second purpose was to examine the impact of possessing a “preferable” polygenic profile on the sport success in terms of the number of medals won in World and National Championships. Finally, we also compared the polygenic profile of world‐ and national‐class Spanish rowers with that of the general Spanish population. The polygenic profile did not differ between groups of rowers. We did not observe an association between having a preferable polygenic profile and medals won in World and National Championships. Finally, we observed that rowers tend to have a more “favorable” polygenic profile than the general Spanish population. These findings argue against the idea that genetic endowment differentiates athletic champions from elite, yet less accomplished athletes. In contrast, we cannot discard the fact that, overall, elite athletes are endowed with a more “favorable” polygenic profile than the general population.

The I allele of the ACE gene is associated with improved exercise capacity in women with McArdle disease

We assessed the possible association existing between alpha-actinin-3 (ACTN3) R577X genotypes and the capacity for performing aerobic exercise in McArdles patients. Forty adult McArdles disease patients and forty healthy, age and gender-matched sedentary controls (21 men, 19 women in both groups) performed a graded test until exhaustion and a constant-load test on a cycle-ergometer to determine clinically relevant indices of exercise capacity as peak oxygen uptake (VO(2peak)) and the ventilatory threshold (VT). In the group of diseased women, carriers of the X allele had a higher (P<0.01) VO(2peak) (15.0+/-1.2 ml/kg/min) and a higher (P<0.05) oxygen uptake (VO(2)) at the VT (11.2+/-1 ml/kg/min) than R/R homozygotes (VO(2peak): 9.6+/-0.5 ml/kg/min; VO(2) at the VT: 8.2+/-0.7 ml/kg/min). No differences were found in male patients. In women with McArdles disease, ACTN3 genotypes might partly explain the large individual variability that exists in the phenotypic manifestation of this disorder.

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.

Genotype Distributions in Top-level Soccer Players: A Role for ACE?

We determined the genotype and allelic frequency of several genetic polymorphisms (ACE I/D, GDF-8K153R [and also E164K, P198A and I225T] and AMPD1 C34T) that are candidates to influence sports performance in a group of 54 male professional soccer players. Their results were compared with those of elite endurance male athletes (52 runners) and 123 sedentary, healthy men (controls). We found statistical significance for the ACE ID (chi (2)((2))=8.176, P=0.017) and II genotypes (chi(2)((2))=16.137, P<0.001) with a higher and lower frequency of ID ( P=0.005) and II (P<0.001), respectively, in soccer players than in endurance runners. Statistical significance was also reached for AMPD1 (with a higher frequency of the CT genotype in soccer players than in runners [chi(2)((2))=7.538, P=0.006]) but not for GDF-8 K153R. Since the ACE II genotype is associated with improved potential for endurance performance but with decreased training gains in muscle mass and strength, these findings together with previous results support the notion that elite soccer players tend to have a power/strength oriented genotype.

‘Smoking Genes’: A Genetic Association Study

Some controversy exists on the specific genetic variants that are associated with nicotine dependence and smoking-related phenotypes. The purpose of this study was to analyse the association of smoking status and smoking-related phenotypes (included nicotine dependence) with 17 candidate genetic variants: CYP2A6*1×2, CYP2A6*2 (1799T>A) [rs1801272], CYP2A6*9 (−48T>G) [rs28399433], CYP2A6*12, CYP2A13*2 (3375C>T) [rs8192789], CYP2A13*3 (7520C>G), CYP2A13*4 (579G>A), CYP2A13*7 (578C>T) [rs72552266], CYP2B6*4 (785A>G), CYP2B6*9 (516G>T), CHRNA3 546C>T [rs578776], CHRNA5 1192G>A [rs16969968], CNR1 3764C>G [rs6928499], DRD2-ANKK1 2137G>A (Taq1A) [rs1800497], 5HTT LPR, HTR2A −1438A>G [rs6311] and OPRM1 118A>G [rs1799971]. We studied the genotypes of the aforementioned polymorphisms in a cohort of Spanish smokers (cases, N = 126) and ethnically matched never smokers (controls, N = 80). The results showed significant between-group differences for CYP2A6*2 and CYP2A6*12 (both P<0.001). Compared with carriers of variant alleles, the odds ratio (OR) for being a non-smoker in individuals with the wild-type genotype of CYP2A6*12 and DRD2-ANKK1 2137G>A (Taq1A) polymorphisms was 3.60 (95%CI: 1.75, 7.44) and 2.63 (95%CI: 1.41, 4.89) respectively. Compared with the wild-type genotype, the OR for being a non-smoker in carriers of the minor CYP2A6*2 allele was 1.80 (95%CI: 1.24, 2.65). We found a significant genotype effect (all P≤0.017) for the following smoking-related phenotypes: (i) cigarettes smoked per day and CYP2A13*3; (ii) pack years smoked and CYP2A6*2, CYP2A6*1×2, CYP2A13*7, CYP2B6*4 and DRD2-ANKK1 2137G>A (Taq1A); (iii) nicotine dependence (assessed with the Fagestrom test) and CYP2A6*9. Overall, our results suggest that genetic variants potentially involved in nicotine metabolization (mainly, CYP2A6 polymorphisms) are those showing the strongest association with smoking-related phenotypes, as opposed to genetic variants influencing the brain effects of nicotine, e.g., through nicotinic acetylcholine (CHRNA5), serotoninergic (HTR2A), opioid (OPRM1) or cannabinoid receptors (CNR1).