Identification of Genomic Predictors of Muscle Fiber Size.

The greater muscle fiber cross-sectional area (CSA) is associated with greater skeletal muscle mass and strength, whereas muscle fiber atrophy is considered a major feature of sarcopenia. Muscle fiber size is a polygenic trait influenced by both environmental and genetic factors. However, the genetic variants underlying inter-individual differences in muscle fiber size remain largely unknown. The aim of our study was to determine whether 1535 genetic variants previously identified in a genome-wide association study of appendicular lean mass are associated with the CSA of fast-twitch muscle fibers (which better predict muscle strength) in the m. vastus lateralis of 148 physically active individuals (19 power-trained and 28 endurance-trained females, age 28.0 ± 1.1; 28 power-trained and 73 endurance-trained males, age 31.1 ± 0.8). Fifty-seven single-nucleotide polymorphisms (SNPs) were identified as having an association with muscle fiber size (p < 0.05). Of these 57 SNPs, 31 variants were also associated with handgrip strength in the UK Biobank cohort (n = 359,729). Furthermore, using East Asian and East European athletic (n = 731) and non-athletic (n = 515) cohorts, we identified 16 SNPs associated with athlete statuses (sprinter, wrestler, strength, and speed-strength athlete) and weightlifting performance. All SNPs had the same direction of association, i.e., the lean mass-increasing allele was positively associated with the CSA of muscle fibers, handgrip strength, weightlifting performance, and power athlete status. In conclusion, we identified 57 genetic variants associated with both appendicular lean mass and fast-twitch muscle fiber size of m. vastus lateralis that may, in part, contribute to a greater predisposition to power sports.

Association analysis of indel variants and gene expression identifies MDM4 as a novel locus for skeletal muscle hypertrophy and power athlete status.

Insertions and deletions (indels) are the second most common type of variation in the human genome. However, limited data on their associations with exercise-related phenotypes have been documented. The aim of the present study was to examine the association between 18,370 indel variants and power athlete status, followed by additional studies in 357,246 individuals. In the discovery phase, the D allele of the MDM4 gene rs35493922 I/D polymorphism was over-represented in power athletes compared with control subjects (P = 7.8 × 10-9) and endurance athletes (P = 0.0012). These findings were replicated in independent cohorts, showing a higher D allele frequency in power athletes compared with control subjects (P = 0.016) and endurance athletes (P = 0.031). Furthermore, the D allele was positively associated (P = 0.0013) with greater fat-free mass in the UK Biobank. MDM4 encodes a protein that inhibits the activity of p53, which induces muscle fibre atrophy. Accordingly, we found that MDM4 expression was significantly higher in the vastus lateralis of power athletes compared with endurance athletes (P = 0.0009) and was positively correlated with the percentage of fast-twitch muscle fibres (P = 0.0062) and the relative area occupied by fast-twitch muscle fibres (P = 0.0086). The association between MDM4 gene expression and an increased proportion of fast-twitch muscle fibres was confirmed in two additional cohorts. Finally, we found that the MDM4 DD genotype was associated with increased MDM4 gene expression in vastus lateralis and greater cross-sectional area of fast-twitch muscle fibres. In conclusion, MDM4 is suggested to be a potential regulator of muscle fibre specification and size, with its indel variant being associated with power athlete status. HIGHLIGHTS: What is the central question of this study? Which indel variants are functional and associated with sport- and exercise-related traits? What is the main finding and its importance? Out of 18,370 tested indels, the MDM4 gene rs35493922 I/D polymorphism was found to be the functional variant (affecting gene expression) and the most significant, with the deletion allele showing associations with power athlete status, fat-free mass and cross-sectional area of fast-twitch muscle fibres. Furthermore, the expression of MDM4 was positively correlated with the percentage of fast-twitch muscle fibres and the relative area occupied by fast-twitch muscle fibres.

Exploring the relationship between caffeine metabolism-related CYP1A2 rs762551 polymorphism and team sport athlete status and training adaptations.

BACKGROUND: This study aimed to achieve a dual objective: to compare the frequencies of CYP1A2 rs762551 genotypes between team sport athletes and a control group, and to determine the association between the rs762551 polymorphism and changes in physical performance after a six-week training program among elite basketball players. METHODS: The study encompassed an analysis of 504 individuals, comprising 320 athletes and 184 controls. For the Turkish cohort, DNA was isolated using the buccal swab method, and genotyping was conducted using the KASP technique. Performance assessments included the Yo-Yo IR2 and 30 m sprint tests. For Russian participants, DNA samples were extracted from peripheral blood, a commercial kit was used for DNA extraction, and genotyping of the rs762551 polymorphism was conducted using DNA microarray. RESULT: Notably, a statistically significant linear decline in the prevalence of the CC genotype was observed with ascending levels of athletic achievement within team sports (sub-elite: 18.0%, elite: 8.2%, highly elite: 0%; p = 0.001). Additionally, the CA genotype was the most prevalent genotype in the highly elite group compared to controls (80.0% vs. 45.1%, p = 0.048). Furthermore, statistically significant improvements in Yo-Yo IR2 performance were noted exclusively among basketball players harboring the CA genotype (p = 0.048). CONCLUSIONS: The study's findings indicate that the rs762551 CC genotype is a disadvantage in elite team sports, whereas the CA genotype provides an advantage in basketball performance.

Effect of ADORA2A Gene Polymorphism and Acute Caffeine Supplementation on Hormonal Response to Resistance Exercise: A Double-Blind, Crossover, Placebo-Controlled Study.

Previous studies have reported that TT genotype carriers of the adenosine A2a receptor (ADORA2A) gene rs5751876 polymorphism have better ergogenic and anti-inflammatory responses to caffeine intake compared to C allele carriers. The aim of the present study was twofold: (1) to investigate the association of the ADORA2A rs5751876 polymorphism with acute caffeine supplementation on hormonal (growth hormone and testosterone) response to resistance exercise (RE); (2) to examine the relationship between the rs5751876 polymorphism and the resting levels of growth hormone and testosterone in athletes who are light caffeine consumers. A double-blind, crossover, placebo-controlled study involving 30 resistance-trained men (age 21.7 ± 4.1) was conducted to assess the impact of caffeine supplementation on serum growth hormone (GH) and testosterone (TS) levels before, immediately after, and 15 min post-RE. One hour before engaging in resistance exercise, subjects were randomly administered 6 mg of caffeine per kg of body mass or a placebo (maltodextrin). After a 7-day washout period, the same protocol was repeated. Resting testosterone and growth hormone levels were examined in the sera of 94 elite athletes (31 females, age 21.4 ± 2.8; 63 males, age 22.9 ± 3.8). Caffeine consumption led to significantly greater increases in GH and TS in men with the TT genotype compared to C allele carriers. Furthermore, in the group of athletes, carriers of the TT genotype had significantly higher testosterone (p = 0.0125) and growth hormone (p = 0.0365) levels compared to C allele carriers. In conclusion, the ADORA2A gene rs5751876 polymorphism may modify the effect of caffeine intake on the hormonal response to exercise.

Effect of the consumption of brazzein and monellin, two recombinant sweet-tasting proteins, on rat gut microbiota.

Sweet-tasting proteins (SPs) are proteins of plant origin initially isolated from tropical fruits. They are thousands of times sweeter than sucrose and most artificial sweeteners. SPs are a class of proteins capable of causing a sweet taste sensation in humans when interacting with the T1R2/T1R3 receptor. SP thaumatin has already been introduced in the food industry in some countries. Other SPs, such as monellin and brazzein, are promising products. An important stage in researching SPs, in addition to confirming the absence of toxicity, mutagenicity, oncogenicity, and allergenic effects, is studying their influence on gut microbiota. In this paper we describe changes in the composition of rat gut microbiota after six months of consuming one of two recombinant SPs-brazzein or monellin. A full length 16S gene sequencing method was used for DNA library barcoding. The MaAsLin2 analysis results showed noticeable fluctuations in the relative abundances of Anaerocella delicata in brazzein-fed rat microbiota, and of Anaerutruncus rubiinfantis in monellin-fed rat microbiota, which, however, did not exceed the standard deviation. The sucrose-fed group was associated with an increase in the relative abundance of Faecalibaculum rodentium, which may contribute to obesity. Overall, prolonged consumption of the sweet proteins brazzein and monellin did not significantly change rat microbiota and did not result in the appearance of opportunistic microbiota. This provides additional evidence for the safety of these potential sweeteners.

Association of ACTN3 R577X Polymorphism with Elite Basketball Player Status and Training Responses.

The α-actinin-3 (ACTN3) gene rs1815739 (C/T, R577X) polymorphism is a variant frequently associated with athletic performance among different populations. However, there is limited research on the impact of this variant on athlete status and physical performance in basketball players. Therefore, the aim of this study was twofold: (1) to determine the association of ACTN3 rs1815739 polymorphism with changes in physical performance in response to six weeks of training in elite basketball players using 30 m sprint and Yo-Yo Intermittent Recovery Test Level 2 (IR 2) tests, and (2) to compare ACTN3 genotype and allelic frequencies between elite basketball players and controls. The study included a total of 363 individuals, comprising 101 elite basketball players and 262 sedentary individuals. Genomic DNA was isolated from oral epithelial cells or leukocytes, and genotyping was performed by real-time PCR using KASP genotyping method or by microarray analysis. We found that the frequency of the ACTN3 rs1815739 XX genotype was significantly lower in basketball players compared to controls (10.9 vs. 21.4%, p = 0.023), suggesting that RR/RX genotypes were more favorable for playing basketball. Statistically significant (p = 0.045) changes were observed in Yo-Yo IRT 2 performance measurement tests in basketball players with the RR genotype only. In conclusion, our findings suggest that the carriage of the ACTN3 rs1815739 R allele may confer an advantage in basketball.

The ADORA2A TT Genotype Is Associated with Anti-Inflammatory Effects of Caffeine in Response to Resistance Exercise and Habitual Coffee Intake.

Caffeine is an adenosine A2A receptor (ADORA2A) antagonist with ergogenic and anti-inflammatory effects. Previous studies have reported that the ADORA2A gene regulates glutamate metabolism and immune responses, with the ADORA2A rs5751876 TT genotype (with high sensitivity to caffeine) showing larger ergogenic effect following caffeine ingestion. We therefore hypothesized that the TT genotype would be associated with greater anti-inflammatory effects of caffeine in response to exercise, and with higher coffee intake in physically active individuals. The aim of the present study was twofold: (1) to investigate the association of the ADORA2A variant with the anti-inflammatory effects of caffeine in response to intense resistance exercise (RE), and (2) to analyze the association of the rs5751876 with coffee intake in physically active individuals (n = 134). Fifteen resistance-trained athletes participated in a randomized, double-blind, placebo-controlled cross-over study, where they consumed 6 mg/kg of caffeine or placebo one hour prior to performing an RE protocol. Blood samples were taken immediately from the arterial vein before, immediately after, and 15 min after RE for the analysis of inflammatory markers myeloperoxidase (MPO) and acetylcholinesterase (AChE). We found that the ADORA2A TT genotype carriers experienced lower exercise-induced inflammatory responses (p < 0.05 for AchE) when compared to the C allele carriers (i.e., CC/CT) one hour following the ingestion of caffeine. Furthermore, the ADORA2A TT genotype was positively associated with coffee intake (p = 0.0143; irrespective of CYP1A2 rs762551 polymorphism). In conclusion, we found that the ADORA2A gene polymorphism is associated with anti-inflammatory effects of caffeine in response to resistance exercise, as well as with habitual coffee intake in physically active individuals.

Exome-Wide Association Study of Competitive Performance in Elite Athletes.

The aim of the study was to identify genetic variants associated with personal best scores in Turkish track and field athletes and to compare allelic frequencies between sprint/power and endurance athletes and controls using a whole-exome sequencing (WES) approach, followed by replication studies in independent cohorts. The discovery phase involved 60 elite Turkish athletes (31 sprint/power and 29 endurance) and 20 ethnically matched controls. The replication phase involved 1132 individuals (115 elite Russian sprinters, 373 elite Russian endurance athletes (of which 75 athletes were with VO2max measurements), 209 controls, 148 Russian and 287 Finnish individuals with muscle fiber composition and cross-sectional area (CSA) data). None of the single nucleotide polymorphisms (SNPs) reached an exome-wide significance level (p < 2.3 × 10-7) in genotype-phenotype and case-control studies of Turkish athletes. However, of the 53 nominally (p < 0.05) associated SNPs, four functional variants were replicated. The SIRT1 rs41299232 G allele was significantly over-represented in Turkish (p = 0.047) and Russian (p = 0.018) endurance athletes compared to sprint/power athletes and was associated with increased VO2max (p = 0.037) and a greater proportion of slow-twitch muscle fibers (p = 0.035). The NUP210 rs2280084 A allele was significantly over-represented in Turkish (p = 0.044) and Russian (p = 0.012) endurance athletes compared to sprint/power athletes. The TRPM2 rs1785440 G allele was significantly over-represented in Turkish endurance athletes compared to sprint/power athletes (p = 0.034) and was associated with increased VO2max (p = 0.008). The AGRN rs4074992 C allele was significantly over-represented in Turkish sprint/power athletes compared to endurance athletes (p = 0.037) and was associated with a greater CSA of fast-twitch muscle fibers (p = 0.024). In conclusion, we present the first WES study of athletes showing that this approach can be used to identify novel genetic markers associated with exercise- and sport-related phenotypes.

KIBRA Gene Variant Is Associated with Ability in Chess and Science.

The kidney and brain expressed protein (KIBRA) plays an important role in synaptic plasticity. Carriers of the T allele of the KIBRA (WWC1) gene rs17070145 C/T polymorphism have been reported to have enhanced spatial ability and to outperform individuals with the CC genotype in working memory tasks. Since ability in chess and science is directly related to spatial ability and working memory, we hypothesized that the KIBRA T allele would be positively associated with chess player status and PhD status in science. We tested this hypothesis in a study involving 2479 individuals (194 chess players, 119 PhD degree holders in STEM fields, and 2166 controls; 1417 males and 1062 females) from three ethnicities (236 Kazakhs, 1583 Russians, 660 Tatars). We found that frequencies of the T allele were significantly higher in Kazakh (66.9 vs. 55.1%; p = 0.024), Russian (44.8 vs. 32.0%; p = 0.0027), and Tatar (51.5 vs. 41.8%; p = 0.035) chess players compared with ethnically matched controls (meta-analysis for CT/TT vs. CC: OR = 2.05, p = 0.0001). In addition, none of the international chess grandmasters (ranked among the 80 best chess players in the world) were carriers of the CC genotype (0 vs. 46.3%; OR = 16.4, p = 0.005). Furthermore, Russian and Tatar PhD holders had a significantly higher frequency of CT/TT genotypes compared with controls (meta-analysis: OR = 1.71, p = 0.009). Overall, this is the first study to provide comprehensive evidence that the rs17070145 C/T polymorphism of the KIBRA gene may be associated with ability in chess and science, with the T allele exerting a beneficial effect.

Genome-Wide Association Study Identifies CDKN1A as a Novel Locus Associated with Muscle Fiber Composition.

Muscle fiber composition is associated with physical performance, with endurance athletes having a high proportion of slow-twitch muscle fibers compared to power athletes. Approximately 45% of muscle fiber composition is heritable, however, single nucleotide polymorphisms (SNP) underlying inter-individual differences in muscle fiber types remain largely unknown. Based on three whole genome SNP datasets, we have shown that the rs236448 A allele located near the cyclin-dependent kinase inhibitor 1A (CDKN1A) gene was associated with an increased proportion of slow-twitch muscle fibers in Russian (n = 151; p = 0.039), Finnish (n = 287; p = 0.03), and Japanese (n = 207; p = 0.008) cohorts (meta-analysis: p = 7.9 × 10−5. Furthermore, the frequency of the rs236448 A allele was significantly higher in Russian (p = 0.045) and Japanese (p = 0.038) elite endurance athletes compared to ethnically matched power athletes. On the contrary, the C allele was associated with a greater proportion of fast-twitch muscle fibers and a predisposition to power sports. CDKN1A participates in cell cycle regulation and is suppressed by the miR-208b, which has a prominent role in the activation of the slow myofiber gene program. Bioinformatic analysis revealed that the rs236448 C allele was associated with increased CDKN1A expression in whole blood (p = 8.5 × 10−15) and with greater appendicular lean mass (p = 1.2 × 10−5), whereas the A allele was associated with longer durations of exercise (p = 0.044) reported amongst the UK Biobank cohort. Furthermore, the expression of CDKN1A increased in response to strength (p < 0.0001) or sprint (p = 0.00035) training. Accordingly, we found that CDKN1A expression is significantly (p = 0.002) higher in the m. vastus lateralis of strength athletes compared to endurance athletes and is positively correlated with the percentage of fast-twitch muscle fibers (p = 0.018). In conclusion, our data suggest that the CDKN1A rs236448 SNP may be implicated in the determination of muscle fiber composition and may affect athletic performance.

Genome-Wide Association Study of Exercise-Induced Fat Loss Efficiency.

There is a wide range of individual variability in the change of body weight in response to exercise, and this variability partly depends on genetic factors. The study aimed to determine DNA polymorphisms associated with fat loss efficiency in untrained women with normal weight in response to a 12-week aerobic training program using the GWAS approach, followed by a cross-sectional study in athletes. The study involved 126 untrained young Polish women (age 21.4 ± 1.7 years; body mass index (BMI): 21.7 (2.4) kg/m2) and 550 Russian athletes (229 women, age 23.0 ± 4.1; 321 men, age 23.9 ± 4.7). We identified one genome-wide significant polymorphism (rs116143768) located in the ACSL1 gene (acyl-CoA synthetase long-chain family member 1, implicated in fatty acid oxidation), with a rare T allele associated with higher fat loss efficiency in Polish women (fat mass decrease: CC genotype (n = 122) -3.8%; CT genotype (n = 4) -31.4%; p = 1.18 × 10-9). Furthermore, male athletes with the T allele (n = 7) had significantly lower BMI (22.1 (3.1) vs. 25.3 (4.2) kg/m2, p = 0.046) than subjects with the CC genotype (n = 314). In conclusion, we have shown that the rs116143768 T allele of the ACSL1 gene is associated with higher fat loss efficiency in response to aerobic training in untrained women and lower BMI in physically active men.

Genomic Predictors of Brisk Walking Are Associated with Elite Sprinter Status.

Brisk walkers are physically more active, taller, have reduced body fat and greater physical fitness and muscle strength. The aim of our study was to determine whether genetic variants associated with increased walking pace were overrepresented in elite sprinters compared to controls. A total of 70 single-nucleotide polymorphisms (SNPs) previously identified in a genome-wide association study (GWAS) of self-reported walking pace in 450,967 European individuals were explored in relation to sprinter status. Genotyping of 137 Russian elite sprinters and 126 controls was performed using microarray technology. Favorable (i.e., high-speed-walking) alleles of 15 SNPs (FHL2 rs55680124 C, SLC39A8 rs13107325 C, E2F3 rs4134943 T, ZNF568 rs1667369 A, GDF5 rs143384 G, PPARG rs2920503 T, AUTS2 rs10452738 A, IGSF3 rs699785 A, CCT3 rs11548200 T, CRTAC1 rs2439823 A, ADAM15 rs11264302 G, C6orf106 rs205262 A, AKAP6 rs12883788 C, CRTC1 rs11881338 A, NRXN3 rs8011870 G) were identified as having positive associations with sprinter status (p < 0.05), of which IGSF3 rs699785 survived correction for multiple testing (p = 0.00004) and was linked (p = 0.042) with increased proportions of fast-twitch muscle fibers of m. vastus lateralis in physically active men (n = 67). Polygenic analysis revealed that individuals with ≥18 favorable alleles of the 15 SNPs have an increased odds ratio of being an elite sprinter when compared to those with ≤17 alleles (OR: 7.89; p < 0.0001). Using UK Biobank data, we also established the association of 14 favorable alleles with low BMI and fat percentage, 8 alleles with increased handgrip strength, and 7 alleles with increased height and fat-free mass. In conclusion, we have identified 15 new genetic markers associated with sprinter status.

Genetic profile of sports climbing athletes from three different ethnicities.

This study aimed to investigate the ACTN3 R577X, ACE I/D, CKM rs8111989, and TRHR rs7832552 genotypes in climbers and controls in three ethnicities. The study consisted of 258 climbers (Japanese, n = 100; Polish, n = 128; Russian, n = 30) and 1151 controls (Japanese: n = 332, Polish: n = 635, Russian: n = 184). Genotyping results were analyzed using the TaqMan approach in Japanese and Polish subjects and HumanOmni1-Quad Bead Chips in Russian subjects. There were no significant differences in ACTN3 R577X and ACE I/D polymorphism distribution between climbers and controls in any ethnic cohort or model. The frequencies of the C allele in the CKM polymorphism and the T allele in the TRHR polymorphism were higher in climbers than in controls only in the Russian cohort (p = 0.045 and p = 0.039, respectively). The results of the meta-analysis on three cohorts showed that the frequency of XX + RX genotypes in the ACTN3 R577X polymorphism was significantly higher in climbers than that in the controls (p = 0.01). The X allele of the ACTN3 R577X polymorphism was associated with sport climbing status, as assessed using a meta-analysis of climbers across three different ethnicities.

Association of Genetically Predicted BCAA Levels with Muscle Fiber Size in Athletes Consuming Protein.

Branched-chain amino acid (BCAA) levels are associated with skeletal muscle cross-sectional area (CSA). Serum BCAA levels are enhanced by whey protein supplementation (WPS), and evidence in clinical populations suggests an association of single nucleotide polymorphisms (SNPs) with BCAA metabolite levels. It is not known whether the same SNPs are associated with the ability to catabolise BCAAs from exogenous sources, such as WPS. The present study investigated whether possessing a higher number of alleles associated with increased BCAA metabolites correlates with muscle fiber CSA of m. vastus lateralis in physically active participants, and whether any relationship is enhanced by WPS. Endurance-trained participants (n = 75) were grouped by self-reported habitual WPS consumption and genotyped for five SNPs (PPM1K rs1440580, APOA5 rs2072560, CBLN1 rs1420601, DDX19B rs12325419, and TRMT61A rs58101275). Body mass, BMI, and fat percentage were significantly lower and muscle mass higher in the WPS group compared to Non-WPS. The number of BCAA-increasing alleles was correlated with fiber CSA in the WPS group (r = 0.75, p < 0.0001) and was stronger for fast-twitch fibers (p = 0.001) than slow-twitch fibers (p = 0.048). Similar results remained when corrected for multiple covariates (age, physical activity, and meat and dairy intake). No correlation was found in the Non-WPS group. This study presents novel evidence of a positive relationship between BCAA-increasing alleles and muscle fiber CSA in athletes habitually consuming WPS. We suggest that a high number of BCAA-increasing alleles improves the efficiency of WPS by stimulation of muscle protein synthesis, and contributes to greater fiber CSA.

Is COL1A1 Gene rs1107946 Polymorphism Associated with Sport Climbing Status and Flexibility?

The purpose of this study was to compare the frequency of COL1A1 rs1107946 polymorphism between sport climbers and controls from three ethnic groups (Japanese, Polish, and Russian) and investigate the effect of the COL1A1 rs1107946 polymorphism on the age-related decrease in flexibility in the general population. Study I consisted of 1929 healthy people (controls) and 218 climbers, including Japanese, Polish, and Russian participants. The results of the meta-analysis showed that the frequency of the AC genotype was higher in climbers than in the controls (p = 0.03). Study II involved 1093 healthy Japanese individuals (435 men and 658 women). Flexibility was assessed using a sit-and-reach test. There was a tendency towards association between sit-and-reach and the COL1A1 rs1107946 polymorphism (genotype: p = 0.034; dominant: p = 0.435; recessive: p = 0.035; over-dominant: p = 0.026). In addition, there was a higher negative correlation between sit-and-reach and age in the AA + CC genotype than in the AC genotype (AA + CC: r = −0.216, p < 0.001; AC: r = −0.089, p = 0.04; interaction p = 0.037). However, none of these results survived correction for multiple testing. Further studies are warranted to investigate the association between the COL1A1 gene variation and exercise-related phenotypes.

Genomic predictors of testosterone levels are associated with muscle fiber size and strength.

PURPOSE: Circulating testosterone levels are a heritable trait with anabolic properties in various tissues, including skeletal muscle. So far, hundreds of single nucleotide polymorphisms (SNPs) associated with testosterone levels have been identified in nonathletic populations. The aim of the present study was to test the association of 822 testosterone-increasing SNPs with muscle-related traits (muscle fiber size, fat-free mass and handgrip strength) and to validate the identified SNPs in independent cohorts of strength and power athletes. METHODS: One hundred and forty-eight physically active individuals (47 females, 101 males) were assessed for cross-sectional area (CSA) of fast-twitch muscle fibers. Significant SNPs were further assessed for fat-free mass and handgrip strength in > 354,000 participants from the UK Biobank cohort. The validation cohorts included Russian elite athletes. RESULTS: From an initial panel of 822 SNPs, we identified five testosterone-increasing alleles (DOCK3 rs77031559 G, ESR1 rs190930099 G, GLIS3 rs34706136 TG, GRAMD1B rs850294 T, TRAIP rs62260729 C) nominally associated (P < 0.05) with CSA of fast-twitch muscle fibers, fat-free mass and handgrip strength. Based on these five SNPs, the number of testosterone-increasing alleles was positively associated with testosterone levels in male athletes (P = 0.048) and greater strength performance in weightlifters (P = 0.017). Moreover, the proportion of participants with ≥ 2 testosterone-increasing alleles was higher in power athletes compared to controls (68.9 vs. 55.6%; P = 0.012). CONCLUSION: Testosterone-related SNPs are associated with muscle fiber size, fat-free mass and strength, which combined can partially contribute to a greater predisposition to strength/power sports.

Polygenic Profile of Elite Strength Athletes.

ABSTRACT: Moreland, E, Borisov, OV, Semenova, EA, Larin, AK, Andryushchenko, ON, Andryushchenko, LB, Generozov, EV, Williams, AG, and Ahmetov, II. Polygenic profile of elite strength athletes. J Strength Cond Res 36(9): 2509-2514, 2022-Strength is a heritable trait with unknown polygenic nature. So far, more than 200 DNA polymorphisms associated with strength/power phenotypes have been identified majorly involving nonathletic populations. The aim of the present study was to investigate individually and in combination the association of 217 DNA polymorphisms previously identified as markers for strength/power phenotypes with elite strength athlete status. A case-control study involved 83 Russian professional strength athletes (53 weightlifters, 30 powerlifters), 209 Russian and 503 European controls. Genotyping was conducted using micro-array analysis. Twenty-eight DNA polymorphisms (located near or in ABHD17C , ACTG1 , ADCY3 , ADPGK , ANGPT2 , ARPP21 , BCDIN3D , CRTAC1 , DHODH , GBE1 , IGF1 , IL6 , ITPR1 , KIF1B , LRPPRC , MMS22L , MTHFR , NPIPB6 , PHACTR1 , PLEKHB1 , PPARG , PPARGC1A , R3HDM1 , RASGRF1 , RMC1 , SLC39A8 , TFAP2D , ZKSCAN5 genes) were identified to have an association with strength athlete status. Next, to assess the combined impact of all 28 DNA polymorphisms, all athletes were classified according to the number of "strength" alleles they possessed. All highly elite strength athletes were carriers of at least 22 (up to 34) "strength" alleles, whereas 27.8% of Russian controls had less than 22 "strength" alleles ( p < 0.0001). The proportion of subjects with a high (≥26) number of "strength" alleles was significantly greater in highly elite strength athletes (84.8%) compared with less successful strength athletes (64.9%; odd ratio [OR] = 3.0, p = 0.042), Russian (26.3%; OR = 15.6, p < 0.0001) or European (37.8%; OR = 6.4, p < 0.0001) controls. This is the first study to demonstrate that the likelihood of becoming an elite strength athlete depends on the carriage of a high number of strength-related alleles.

The BDNF-Increasing Allele is Associated With Increased Proportion of Fast-Twitch Muscle Fibers, Handgrip Strength, and Power Athlete Status.

ABSTRACT: Guilherme, JPLF, Semenova, EA, Borisov, OV, Kostryukova, ES, Vepkhvadze, TF, Lysenko, EA, Andryushchenko, ON, Andryushchenko, LB, Lednev, EM, Larin, AK, Bondareva, EA, Generozov, EV, and Ahmetov, II. The BDNF-increasing allele is associated with increased proportion of fast-twitch muscle fibers, handgrip strength, and power athlete status. J Strength Cond Res 36(7): 1884-1889, 2022-The brain-derived neurotrophic factor (BDNF) is involved in neurogenesis and formation of regenerated myofibers following injury or damage. A recent study suggested that the BDNF overexpression increases the proportion of fast-twitch muscle fibers, while the BDNF deletion promotes a fast-to-slow transition. The purpose of this study was to evaluate the association between the BDNF gene rs10501089 polymorphism (associated with blood BDNF levels), muscle fiber composition, and power athlete status. Muscle fiber composition was determined in 164 physically active individuals (113 men, 51 women). BDNF genotype and allele frequencies were compared between 508 Russian power athletes, 178 endurance athletes, and 190 controls. We found that carriers of the minor A-allele (the BDNF-increasing allele) had significantly higher percentage of fast-twitch muscle fibers than individuals homozygous for the G-allele (males: 64.3 [7.8] vs. 50.3 [15.8]%, p = 0.0015; all subjects: 64.1 ± 7.9 vs. 49.6 ± 14.7%, p = 0.0002). Furthermore, the A-allele was associated (p = 0.036) with greater handgrip strength in a sub-group of physically active subjects (n = 83) and over-represented in power athletes compared with controls (7.7 vs. 2.4%, p = 0.0001). The presence of the A-allele (i.e., AA+AG genotypes) rather than GG genotype increased the odds ratio of being a power athlete compared with controls (odds ratio [OR]: 3.43, p = 0.00071) or endurance athletes (OR: 2.36, p = 0.0081). In conclusion, the rs10501089 A-allele is associated with increased proportion of fast-twitch muscle fibers and greater handgrip strength, and these may explain, in part, the association between the AA/AG genotypes and power athlete status.

CKM Gene rs8111989 Polymorphism and Power Athlete Status.

Multiple genetic variants are known to influence athletic performance. These include polymorphisms of the muscle-specific creatine kinase (CKM) gene, which have been associated with endurance and/or power phenotypes. However, independent replication is required to support those findings. The aim of the present study was to determine whether the CKM (rs8111989, c.*800A>G) polymorphism is associated with power athlete status in professional Russian and Lithuanian competitors. Genomic DNA was collected from 693 national and international standard athletes from Russia (n = 458) and Lithuania (n = 235), and 500 healthy non-athlete subjects from Russia (n = 291) and Lithuania (n = 209). Genotyping for the CKM rs8111989 (A/G) polymorphism was performed using PCR or micro-array analysis. Genotype and allele frequencies were compared between all athletes and non-athletes, and between non-athletes and athletes, segregated according to population and sporting discipline (from anaerobic-type events). No statistically significant differences in genotype or allele frequencies were observed between non-athletes and power athletes (strength-, sprint- and speed/strength-oriented) athletes. The present study reports the non-association of the CKM rs8111989 with elite status in athletes from sports in which anaerobic energy pathways determine success.

The MCT1 gene Glu490Asp polymorphism (rs1049434) is associated with endurance athlete status, lower blood lactate accumulation and higher maximum oxygen uptake.

The purpose of this study was to explore the association of the MCT1 gene Glu490Asp polymorphism (rs1049434) with athletic status and performance of endurance athletes. A total of 1,208 Brazilians (318 endurance athletes and 890 non-athletes) and 867 Europeans (315 endurance athletes and 552 non-athletes) were evaluated in a case-control approach. Brazilian participants were classified based on self-declared ethnicity to test whether the polymorphism was different between Caucasians and Afro-descendants. Moreover, 66 Hungarian athletes underwent an incremental test until exhaustion to assess blood lactate levels, while 46 Russian athletes had their maximum oxygen uptake ( V ⋅ O 2 max ) compared between genotypes. In the Brazilian cohort, the major T-allele was more frequent in Caucasian top-level competitors compared to their counterparts of lower competitive level (P = 0.039), and in Afro-descendant athletes compared to non-athletes (P = 0.015). Similarly, the T-allele was more frequent in European athletes (P = 0.029). Meta-analysis of the Brazilian and European cohorts confirmed that the T-allele is over-represented in endurance athletes (OR: 1.48, P = 0.03), especially when Afro-descendant athletes were included in the meta-analysis (OR: 1.58, P = 0.005). Furthermore, carriers of the T/T genotype accumulated less blood lactate in response to intense effort (P < 0.01) and exhibited higher V ⋅ O 2 max (P = 0.04). In conclusion, the Glu490Asp polymorphism was associated with endurance athletic status and performance. Our findings suggest that, although ethnic differences may exist, the presence of the major T-allele (i.e., the Glu-490 allele) favours endurance performance more than the mutant A-allele (i.e., the 490-Asp allele).