European Human Genetics Conference (abstract database)
The ACE I/D polymorphism in Lithuanian professional athletes
V. Ginevic(iene.1,2, J. Kasnauskiene.1, V. Kuc(inskas1;
1Department of Human and Medical Genetics, Faculty of Medicine, Vilnius University, Vilnius, Lithuania, 2Lithuanian Olympic Sports Centre, Vilnius, Lithuania.
Presentation Number: P07.002
Human physical performance is under strong influence of genetic factors. I/D polymorphism in the human angiotensin-1-coverting enzyme (ACE) gene characterised by the presence (I allele) or absence (D allele) of a 287-base-pair Alu repeat within intron 16 is among most extensively investigated ones with respect to ACE activity and its involvement in various pathophysiological conditions related to endurance. Nevertheless, the results are still conflicting across studies and populations. In the present study, ACE gene I/D polymorphism was investigated in 413 Lithuanian professional athletes representing four functional groups [endurance (N=57); mixed sports (N=44); strength and speed (N=30), and team sports (N=282)], as well as in 120 samples from general population of Lithuanians. Statistically significantly higher D allele frequencies were found in strength and speed group (P=0.02) as well as in endurance group (P=0.06), contrary to the prevailing data from other studies showing association of endurance with I allele. D allele also appeared to be more frequent in the general population of Lithuanians (60,4 %) in comparison to the majority of other European populations (30-50%). Thus, increased D allele prevalence in strength and speed group of athletes from Lithuania can be a reflection of population frequency of this allele. In conclusion, our results imply that the role of ACE gene I/D polymorphism in athletic performance is not straightforward and can be masked by other genetic and non-genetic factors.
Association of the ACTN3 gene variant with endurance athlete status
A. M. Druzhevskaya, I. I. Ahmetov, I. V. Astratenkova, V. A. Rogozkin;
St Petersburg Research Institute of Physical Culture, St Petersburg, Russian Federation.
Presentation Number: P07.003
Alpha-actinin-3 (ACTN3) is a myofibrillar protein found in fast-twitch glycolytic muscle fibers. The less common X-allele of the R577X polymorphism in the ACTN3 gene results in a premature stop codon and alpha-actinin-3 protein deficiency in XX homozygotes. A strong association has been reported between the R577X polymorphism and elite athletic performance. The aim of the study was to investigate genotype and allele distribution of ACTN3 gene in endurance-oriented athletes and controls. The study involved 501 athletes (biathletes; rowers; long distance runners, swimmers and skaters, road cyclists, skiers, triathletes, race walkers) and 1197 controls. Genotyping was performed by restriction fragment length polymorphism analysis. The distribution of ACTN3 genotypes (athletes: RR - 37.1%, RX - 53.1%, XX - 9.8%; controls: RR - 36.8%, RX - 49.0%, XX - 14.2%) was significantly different between athletes and controls (P=0.038). While R allele frequency did not differ between athletes (63.7%) and controls (61.3%), the frequency of XX genotype was under-represented in athletes compared to controls (9.8% vs. 14.2%, P=0.013). We therefore conclude that XX genotype is unfavorable for endurance performance.
HIF1A gene polymorphism is associated with power performance in athletes
A. M. Hakimullina, I. I. Ahmetov, V. A. Rogozkin;
St Petersburg Research Institute of Physical Culture, St Petersburg, Russian Federation.
Presentation Number: P06.129
Glycolysis is the central source of anaerobic energy in humans, and this metabolic pathway is regulated under low-oxygen conditions by the transcription factor hypoxia-inducible factor 1a (HIF-1a). HIF-1a controls a number of genes that are implicated in various cellular functions including cell proliferation (erythropoietin), glucose metabolism (glucose transporters and glycolytic enzymes), cell survival, and angiogenesis (vascular endothelial growth factor and VEGF receptors). A missense polymorphism, Pro582Ser, is present in exon 12 (C/T at bp 85). The rare T-allele is predicted to result in a proline to serine change in the amino acid sequence of the protein. This substitution increases protein stability and transcriptional activity, and therefore, improves glucose metabolism and angiogenesis. In this study, we investigated whether genetic variation at the locus encoding HIF1A is associated with elite athlete status in weightlifters, for which glycolysis is crucial for power performance. The study involved 53 Russian athletes (17 sub-elite, 32 elite and 4 highly elite) and 920 controls. HIF1A gene Pro582Ser polymorphism was determined by PCR-RLFP. The frequency of the rare Ser allele was significantly higher in weightlifters than in controls (17.9% vs. 8.5%; P=0.001). Moreover, the frequency of Ser allele increased with growing skill level of athletes (sub-elite (14.7%) - elite (18.8%) - highly elite (25.0%)). Thus, HIF1A gene Pro582Ser polymorphism is associated with elite power athlete status, which suggests an important role for HIF-1a in skeletal muscle adaptation to power training.
The ability to become an elite endurance athlete depends on the carriage of high number of endurance-related alleles
I. I. Ahmetov, A. M. Hakimullina, J. V. Shikhova, I. A. Mozhayskaya, V. A. Rogozkin;
St Petersburg Research Institute of Physical Culture, St Petersburg, Russian Federation.
Presentation Number: P06.233
The objective was to evaluate the total contribution of CNB, NFATC4, PGC1A, PGC1B, TFAM, VEGF, UCP2, UCP3 gene alleles in defining predisposition to sports. The study involved 1580 Russian athletes and 1057 controls. CNB (calcineurin B) 5I/5D, NFATC4 (nuclear factor of activated T-cells, calcineurin-dependent 4) Ala160Gly, PGC1A (PPARgamma coactivator-1-alpha) Gly482Ser, PGC1B (PPARgamma coactivator-1-beta) Ala203Pro, TFAM (transcription factor A, mitochondrial) Thr12Ser, VEGF (vascular endothelial growth factor) G-634C, UCP2 (uncoupling protein 2) Ala55Val, UCP3 (uncoupling protein 3) -55C/T gene polymorphisms were determined by PCR-RLFP. We found that the frequency of endurance-related alleles (CNB I, NFATC4 Gly, PGC1A Gly, PGC1B Pro, TFAM Thr, VEGF C, UCP2 Val, UCP3 T) were significantly higher in Russian elite endurance-oriented athletes (n=351) compared to controls, both separately and cumulatively (45.6% vs. 37.4%, p<0.0001). Furthermore, 66.7% of highly elite endurance-oriented athletes (Olympic and World championship winners; n=12) were carriers of 8 to 12 endurance-related alleles (the others were carriers of 7 alleles), while there were only 18.1% of such persons in the control group (p<0.0001). Thus, the success in sports can be attributed to the carriage of high number of alleles associated with certain physical qualities.
NFATC4 gene polymorphism and aerobic performance in athletes
D. V. Popov1, I. I. Ahmetov2, J. V. Shikhova2, S. S. Missina1, O. L. Vinogradova1, V. A. Rogozkin2;
1SRC Institute for Biomedical Problems of the Russian Acad. Sci., Moscow, Russian Federation, 2St Petersburg Research Institute of Physical Culture, St Petersburg, Russian Federation.
Presentation Number: P06.209
Nuclear factor of activated T cells C4 gene (NFATC4) encodes transcription factor which regulates cardiac and skeletal muscle metabolism. The aim of the study was to investigate allelic distribution of NFATC4 gene Gly160Ala polymorphism in endurance-oriented athletes (n=549) and controls (n=1057), and to find interrelation between genotypes and physiological parameters in rowers (n=90). Genotyping was performed by restriction fragment length polymorphism analysis. Physiological parameters were evaluated by PM 3 Rower Ergometer and MetaMax 3B Gas Analyzer. The frequency of NFATC4 Gly allele was significantly higher in athletes than in controls (51.5% vs. 43.7%; p<0.0001), and increased with the growth of skills (sub-elite athletes: 36.7%-48.5%; highly elite athletes: 60.6%-62.5%). Furthermore, NFATC4 Gly allele was associated with high values of aerobic performance (when VO2max and AT in % of VO2max were measured). Thus, NFATC4 gene Gly160Ala polymorphism is associated with aerobic performance of athletes and plays an important role in sports selection.
VEGF A2578C polymorphism is associated with muscle fiber type distribution in athletes
E. V. Lyubaeva1, I. I. Ahmetov2, A. M. Hakimullina2, O. L. Vinogradova1, V. A. Rogozkin2;
1SRC Institute for Biomedical Problems of the Russian Acad. Sci., Moscow, Russian Federation, 2St Petersburg Research Institute of Physical Culture, St Petersburg, Russian Federation.
Presentation Number: P06.309
There is strong relationship between muscle fiber type distribution and human physical performance. For example, elite weightlifters and sprinters exhibit large percentages of fast-twitch fibers (FT, also known as type II muscle fibers) compared to controls and endurance athletes. FT fibers have comparatively low capillary density and blood flow capacity and low mitochondria content. Vascular endothelial growth factor (VEGF) is important in the basal maintenance of skeletal muscle capillarization and may influence the determination of muscle fiber type distribution. To investigate the question of the influence of VEGF gene polymorphism on the proportion of fibers types of m. vastus lateralis, we have analyzed the muscle biopsies obtained from 21 elite Russian athletes (all-round speed skaters). The immunoperoxidase technique was employed for immunohistochemical identification of myosin isoforms. VEGF gene A2578C polymorphism was determined by PCR-RLFP. Mean percentages of FT fibers were significantly higher in VEGF CC homozygotes than in VEGF A allele carriers (AA/AC - 38.3 (6.2) %, CC - 47.8 (12.4) %; P=0.03). Then we determined distribution of VEGF alleles in 60 elite and sub-elite weightlifters and in 1,113 controls. We found that the frequency of VEGF 2578C allele was significantly higher in weightlifters than in controls (58.3% vs. 48.0%; P=0.035). In conclusion, VEGF 2578C allele is associated with increased proportion of FT muscle fibers in all-round speed skaters and with elite power athlete status.
UCP3 gene polymorphism and cardiac growth in response to 1 year of endurance training
S. B. Goriyeva1, I. I. Ahmetov1,2, O. L. Vinogradova1;
1SRC Institute for Biomedical Problems of the Russian Acad. Sci, Moscow, Russian Federation, 2St Petersburg Research Institute of Physical Culture, St Petersburg, Russian Federation.
Presentation Number: P06.300
Reduced fatty acid utilization and increased oxidative stress both can contribute to the development of cardiac hypertrophy. Left ventricular hypertrophy in endurance-oriented athletes is generally understood to be a limiting factor for improving maximal oxygen uptake (VO2max). Cardiac uncoupling protein 3 (UCP3) can serve to protect the heart against lipid-induced oxidative stress, and stimulate fatty acid transport and oxidation. A variant in the UCP3 gene associated with higher mRNA levels has been identified (UCP3 -55C/T). This variant has been associated with reduced risk of type 2 diabetes and obesity. Recently we have shown that -55T allele was overrepresented in highly elite rowers and was associated with high values of VO2max. If UCP3 is important for muscle and heart metabolism and can protect against development of LVH, then one might anticipate -55T variant of UCP3 gene to be associated with insignificant cardiac growth (rational adaptation) in response to endurance training. We have tested this hypothesis in the study of elite Russian rowers (n=19, males). UCP3 -55C/T polymorphism was determined by PCR-RLFP. Echocardiography was performed for two times with one year interval. We found that subjects of CC genotype exhibited the greatest cardiac growth (when interventricular septal wall thickness was measured; CC: 3 (1.4) mm, CT: 1 (0) mm, TT: -1 mm; P=0.019), whereas the individuals of TT genotype exhibited the reduction in septal wall thickness. In conclusion, we demonstrate that variation in the UCP3 gene influences cardiac growth in response to endurance training in rowers.
The interaction between gene polymorphisms and carbohydrate intake on metabolic profile in Russian athletes
A. A. Topanova, I. I. Ahmetov, R. R. Dondukovskaya, N. D. Golberg;
St Petersburg Research Institute of Physical Culture, St Petersburg, Russian Federation.
Presentation Number: P06.212
Genetic and nutritional factors interact together and modulate the plasma carbohydrate and lipid profile. The objective was to study whether carbohydrate intake modulates the association between NFATC4, PGC1A, PPARA, PPARG, PPARD, TFAM, UCP2 and UCP3 gene variations and metabolic profile in Russian athletes. The study involved 33 male Russian sub-elite endurance-oriented athletes (road cyclists), who were randomly assigned to consume carbohydrates/minerals (CARB, n=17; 6% 200 ml drink “Olympia” (Estonia)) or placebo (CON, n=16; 200 ml pure water) for 20 d at 20th min from the end of evening training. Plasma concentrations of total cholesterol, glucose and resting lactate (La) were evaluated in the morning before and at the end of experiment. NFATC4 Ala160Gly, PGC1A Gly482Ser, PPARA G/C, PPARG Pro12Ala, PPARD +294T/C, TFAM Thr12Ser, UCP2 Ala55Val, UCP3 -55C/T gene polymorphisms were determined by PCR-RLFP. At base-line PPARA C allele carriers exhibited the highest values of La (P=0.008); NFATC4 Ala (P=0.04) and TFAM Ser (P=0.024) alleles were associated with higher glucose concentrations. At the end of experiment PGC1A Ser (r=0.54, P=0.03), PPARG Pro (r=0.58, P=0.019) alleles were positively correlated with high values of La in CARB- and CON-groups, respectively, whilst PPARD C allele (r=0.47, P=0.055) was associated with higher total cholesterol levels in CARB-group. Furthermore, PPARG Pro allele carriers of CARB-group showed the greatest decrease in total cholesterol. Thus, polymorphisms of PGC1A, PPARG and PPARD genes (involved in carbohydrate and lipid metabolism) may interact with carbohydrate intake to modulate metabolic profile of endurance-oriented athletes.
Polymorphisms in ACTN3, ACE and AMPD1 genes and physical performance in Bulgarian sub-elite athletes
S. A. Andonov1, R. Saraeva2, S. Andonova2,3, R. Kaneva2,3, V. Gigova1, L. Stefanov1, I. Kremensky2,3, P. Atanasov1;
1National Sports Academy “Vassil Levski”, Sofia, Bulgaria, 2Molecular Medicine Center, Medical University, Sofia, Bulgaria, 3University Hospital of Obstetrics, Sofia, Bulgaria.
Presentation Number: P06.004
The aim of this study was to analyse ACTN3 (R577X), ACE (I/D) and AMPD1 (34C>T) polymorphisms in sub-elite athletes (n=70, 57 males and 13 females) and controls (n=44, 15 males and 29 females). The correlations between genotypes and physiological and biochemical parameters at anaerobic conditions was investigated. Athletes were divided into three sport groups according to a power-time model of performance intensity. The physiological parameters were evaluated by standard Wingate Anaerobic Test and Ergospirometry. Spectrophotometry and Blood-Gas analysis were used for the estimation of the glycolytic enzyme activity of Lactate Dehydrogenase and Acid-Base Balance, respectively. DNA samples was genotyped by RFLP analysis followed by agarose gel-electrophoresis. Differences in the distribution of alleles and genotypes between the groups were assessed by x2-test. Statistical analysis of variances was performed using one way ANOVA. No significant differences between the athletes and controls was found according the allele and genotype frequencies of the investigated polymorphisms. AMPD1 heterozygous male athletes in the “Anaerobic” group showed greater Mean Power Output (Watts) in comparison to CC homozygous athletes (9,11 vs. 7,34 Watts). Significant correlation was observed also with the buffering capacity (HCO3 and BE). No Individuals homozygous for the T-allele of AMPD1 were found. The ACTN3 genotype correlated with parameters relevant to exercise capacity such as oxygen uptake, saturation and Lean Body Mass in the male sub-groups of anaerobic sports and endurance sports, but not in the female sub-groups.
Skeletal Muscle Gene ACTN3 and Physical Performance:
O. Kas?may1, D. Sevinc2, S. O. Iseri1, K. Ulucan3, M. Unal1, A. I. Guney4, H. Kurtel1;
1Marmara University, School of Medicine, Sport Physiology Department, Istanbul, Turkey, 2Maltepe University, School of Medicine, Medical Biology and Genetics Department, Istanbul, Turkey, 3Marmara University, School of Dentistry, Medical Biology and Genetics Department, Istanbul, Turkey, 4Marmara University, School of Medicine, Medical Genetics Department, Istanbul, Turkey.
Presentation Number: P07.046
ACTN3 gene is responsible from the production of alpha-actinin-3 protein, which has force-generating capacity of muscle fibers, and which is restricted to fast fibers. Homozygosity for 577X in ACTN3 (R577XX) results in no production of a-actinin-3 protein. Recent studies show that elite sprint athletes had a higher frequency of the RR genotype. Aim: The purpose of the study was to investigate ACTN3 gene variations and their probable phenotypic reflection by using physiological methods, and to show ACTN3 polymorphism in Turkish soccer players (n=31). Methods: After determining the genotypes by analyzing the blood samples, three groups (XX,RR,RX) were formed. The groups were existing R577X variant in both ACTN3 genes (XX,n=4), not existing R577X variant in both ACTN3 genes (RR,n=22), or existing R577X variant only one of the two ACTN3 genes (RX,n=5), respectively. To determine aerobic performance, Bruce protocol was applied on treadmill and maximal oxygen consumption (VO2max) was measured by metabolic analyzer. On a separate day, anaerobic performance was evaluated by Wingate test. Student’s t-test or analysis of variance (ANOVA) was used for comparisons. Results: Thirteen % of the soccer players had homozygosity for R577XX codon. The VO2max levels in XX group tended to be higher from RR (p=0.09) and RX groups (p=0.05). VO2/HR (pulse oxygen) and VEmax (maximum ventilation) levels were not different between groups. Peak power values tended to be higher in RR group from the other groups. Our results evaluated the effect of genotypic variations on sprint and endurance performance of athletes contributing the understanding of genotype-phenotype correlation.
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