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Medicine & Science in Sports & Exercise:
doi: 10.1249/01.mss.0000433616.43803.97

A-41 Free Communication/Poster - Genetics

Free Access

May 29, 2013, 7:30 AM - 12:30 PM

Room: Hall C

278 Board #130 May 29, 9:30 AM - 11:00 AM

Effects Of Dopamine D2 Receptor Gene Polymorphism On Physical Activity Level In Humans

Haruka Murakami1, Motoyuki Iemitsu2, Kiyoshi Sanada2, Noriyuki Fuku3, Ryoko Kawakami1, Yuko Gando4, Motohiko Miyachi1. 1National institute of Health and Nutrition, Tokyo, Japan. 2Ritsumeikan University, Shiga, Japan. 3Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan. 4Waseda University, Saitama, Japan.

(No relationships reported)

Voluntary physical activity is important to human health, including prevention of non-communicable diseases. Twin studies have found that genetic factors play a role in physical activity and exercise habit. However, there have been few reports regarding specific genes involved in determining physical activity level in humans.

PURPOSE: This study was performed to investigate the association between physical activity level and polymorphism of the dopamine D2 receptor gene (DRD2/ANKK1), which plays a role in movement control as well as in reward mechanisms.

METHODS: Subjects were recruited from among the total population of 1057 included in the Nutrition and EXercise Intervention Study (NEXIS). Subjects were assessed for their mean daily amount of physical activity for 14 days by triaxial accelerometry and their involvement in physical activity and sports over the past year using a questionnaire. In addition, peak oxygen uptake (VO2peak) was assessed by incremental cycle excise test. Metabolic risk factors and degree of arteriosclerosis were also measured. A total of 467 Japanese men and women participated in the study and their DRD2/ANKK1 genotypes were determined. Subjects with a history of stroke, cardiac disease, chronic renal failure, or chronic knee or back pain, over 60 years old, and for whom no physical activity data were available were excluded.

RESULTS: The genotype frequencies were 41.3% CC, 45.2% CT, 13.5% TT. No associations between DRD2/ANKK1 genotype and metabolic risk factors or degree of arteriosclerosis were observed. In addition, there were no associations between DRD2/ANKK1 genotype and any physical activity index assessed by accelerometry. There were no significant differences in genotype frequencies between the two groups of subjects divided according to median of each physical activity index.

CONCLUSIONS: The results suggested that DRD2/ANKK1 genotype is not associated with physical activity level. However, it is necessary to investigate the association between long periods of physical activity and DRD2/ANKK1 genotype.

279 Board #131 May 29, 9:30 AM - 11:00 AM

SLC 16A1 Gen Polymorphism in Relation to Blood Lactate Concentration in Endurance Athletes

M Soria1, J Vicente1, C González-Haro1, G Conefrey2, A Fanlo1, JF Escanero1, B Sinués1. 1School of Medicine. University of Zaragoza, Zaragoza, Spain. 2Health Sciences, University College Dublin, Dublin, Ireland.

(No relationships reported)

Blood lactate clearance (BLC) is one of the most important long-term adaptations in elite/professional endurance athletes. Membrane lactate transporters, such as MCT 1, play a vital role in the influx and efflux of lactate across fiber muscle plasma membranes. Recently, it has been suggested that mutations in this transporter could be associated with lactate transport deficiency. 1470T>A polymorphism (rs 1049434) carriers have been related with a lower BLC capacity. It would be interesting to study the relationship of other polymorphisms in relation with the lactate metabolism in athletes.

PURPOSE: To study the association between variants in the SLC 16A1 gene frequency in relation to blood lactate concentration ([La-]b) during an incremental protocol in endurance athletes.

METHODS: 27 well-trained endurance athletes (age: 33.8 ± 6.7 yr) carried out a warm-up on cycloergometer of 10 min at 2.0 w·kg-1 and increments of 0.5 w·kg-1 every 10 min until the exhaustion. [La-]b was measured at rest, at the end of each stage and at 3rd, 5th and 7th min post-exercise. Genomic DNA was analysed by quantitative real time reverse transcription polymerase chain reaction (RT-PCR), measuring fragments containing 1470T>A polymorphism (rs 1049434), 2917C>T polymorphism (rs7169) and IVs3-17A>C polymorphism. The Mann Whitney U test was performed to analyse the differences between carrier/non-carrier (subjects who presented their two wild-type alleles) of each polymorphism at every intensity of exercise. Significance level was set at P<0.05.

RESULTS: Wild-type, heterozygotes and mutated homozygotes genotype distribution were 36%, 60% and 4% for 1470T>A; 60%, 40% and 0% for 2917C>T; 28%, 72% and 0% for IVS3-17A>C. The carrier group presented higher values of [La-]b than the non-carrier group (P<0.01) at rest, at every intensity of exercise assessed and at the 3rd, 5th and 7th min post-exercise, for the three polymorphisms studied.

CONCLUSIONS: Carriers of the three polymorphisms studied at the present research expressed higher amounts of blood lactate concentration. This suggests that blood lactate clearance is worse in athletes carrying the variants/mutations of SLC 16A1 studied at the present research.

280 Board #132 May 29, 9:30 AM - 11:00 AM

Comparison Of Exercise-Induced Metabolic Acidosis Between Miltenberger Blood Group Antigen Type III (MiIII) And Non-MiIII Athletes

Tso-Yen Mao1, Pei-Fan Wang2, Yi-Tzu Chen2, Kate Hsu1, Li-Lan Fu2. 1Mackay Memorial Hospital, Tamsui, Taiwan. 2National Taiwan Sport University, Taoyuan, Taiwan.

(No relationships reported)

Milterberger blood group antigen type III (MiIII) is an important blood type in Taiwan. Red blood cells expressing MiIII have been shown to be more resilient in acidosis.

PURPOSE: To compare the level of metabolic acidosis following intensive exercise between MiIII and non- MiIII athletes.

METHODS: 7 MiIII athletes and 15 non-MiIII athlete controls with similar anthropometric conditions were recruited from the National Taiwan Sport University baseball team (MiIII: 180.1±2.9cm, 81.4±10.3kg, 20.1±1.1yr; non-MiIII: 177.5±3.2cm, 76.3±8.3kg, 20.3±0.9yr). The maximal exercise tests were performed using a treadmill, and the cardiopulmonary data (HR, VE, VO2 and VCO2) and the concentrations of metabolic blood lactate were collected simultaneously.

RESULTS: The MiIII athletes had higher levels of blood lactate than the non-MiIII athletes immediately after the maximal exercise tests (14.1±3.6 vs. 11.8±2.3 mmol.L-1, p<0.05). Further, MiIII athletes appeared to reach the onset of ventilator threshold (calculated from the V slope) at earlier time points during the maximal exercise tests than the non-MiIII (673±82 vs. 735±75 seconds, p<0.05).

CONCLUSION: The MiIII athletes appear to prefer to switch to anaerobic means of energy production at earlier time points than the non-MiIII athletes during the maximal exercise tests. This observation is in accordance with the greater tolerance of metabolic acidosis in Miltenberger red cells. Supported by NHRI-EX101-10122SI.

281 Board #133 May 29, 9:30 AM - 11:00 AM

Association Between Energy Metabolism Of The Actn3 Heterozygous Genotype And Physical Fitness Tests

Arturo Orozco-Díaz, José Moncada-Jiménez, Gabriela Chavarría, Alejandro Leal. Universidad de Costa Rica, San José, Costa Rica.

(No relationships reported)

Athletic performance is a complex human trait influenced by genetics and the environment. A nonsense mutation Arg577X, a single base transversion C→T sustitution in exon 16 of the ACTN3 gen converts an Arginine residue to a stop o codon (X) at 577 amino acid position. Although several studies exist on athletes, research in non-athletic individuals is lacking.

PURPOSE:To study the association between the ACTN3 genotypes and the physical performance on non-athletic Costa Rican individuals.

METHODS: Non-athletic college students volunteers were 13 men (Mean height = 172.7 ± 5.3 cm; weight = 67.6 ±12.6 kg) and 27 women (Mean height= 160.4 ± 8.6 cm; weight = 59.1 ± 10.6 kg). A 4-ml blood sample was obtained from each participant. DNA was extracted using the phenol-chloroform method and PCR analysis was used to amplify the 303 bp fragment containing the gene mutation. ACTN3 genotypes were determined by enzymatic digestion of the PCR products with DdeI. Aerobic power (VO2 max), vertical jump (Squat Jump = SJ; Counter movement Jump = CMJ) and anaerobic power (Wingate Test; TPP = time to peak power; MP = Mean power; PP = peak power) were completed by each individual in one single session.

RESULTS: Genotype distribution on this sample of individuals was RR= 52.5%, RX= 35%, and XX=12.5%. An effect of the ACTN3 R577X polymorphism XX on the study phenotypes was observed. A one-way ANOVA coding the genotype as the between-subjects factor revealed significant mean (M) differences in VO2max performance (p = 0.030). Tukey HSD post hoc analysis indicated that VO2max was higher in the XX (M= 42.46 ± 13.98 ml/kg/min) compared to RX (M= 33.09 ± 9.39 ml/kg/min) and RR (M= 30.48 ± 6.55 ml/kg/min) polymorphisms (p < 0.05). No significant between-group differences were found for CMJ (M=32.9±6.0 cm, p=0.584), SJ (M=30.0±6.8 cm, p=0.258), TPP (M=1.3±0.5 s, p=0.771), MP (M=363.6±135.5 W, p= 0.072), and PP (M=614.1±292.2 W, p=0.196).

CONCLUSIONS: An association between the genotype XX of the ACTN3 gen and the VO2max performance was observed in this study. Non-athletic individuals carrying the XX genotype had a better performance in endurance fitness than individuals carrying the R allele, either in heterozygous or homozygous form. A larger sample size will allow us to determine if associations of these genes exist on other athletic performance variables.

282 Board #134 May 29, 9:30 AM - 11:00 AM

Association between Ghrelin Precursor Gene Variants and Fluid Intake in 42-km Runners

Christian A. Torrech1, Juan L. Martinez-Barreda2, Thomas D. Fahey3, Miguel A. Rivera, FACSM1. 1University of Puerto Rico, San Juan, PR. 2Hospital Civil de Culiacán, Culiacán, Mexico. 3California State University, Chico, Chico, CA.

(No relationships reported)

Ghrelin is a 28 amino acid peptide chain predominantly found in the stomach. Recent studies indicate that ghrelin may influence fluid intake regulation. We recently reported (MSSE 44(5S): 441, 2012) an association between a ghrelin single-nucleotide polymorphism (SNP) and fluid intake in 10-km runners.

PURPOSE: We examined the hypothesis of association between the ghrelin precursor gene (GHRL) and fluid intake in marathon runners.

METHODS: The subjects (n=90) were apparently healthy biologically unrelated Hispanic male recreational long distance runners (Age = 27 ± 4 yr; Ht = 168 ± 12 cm; Wt = 63 ± 6 kg; mean ± SD). Data were collected before and after an international 42-km road race. For each subject a “race number labeled” 500 mL water bottle was available at 5-km intervals. Fluid intake was ad libitum and calculated by measuring the weight of bottles before and after fluid ingestion. Genomic DNA was extracted from whole blood (8mL) using the Promega Wizard Genomic DNA Purification Kit. Three SNPs were genotyped: rs35684 (A/G: a transition substitution in exon 1), rs2075356 (C/T: intron), and rs26311 (A/G: near the 3’ untranslated region) of GHRL. Genotypes were determined by PCR product size. ANOVA was used to calculate whether the fluid intake means by GHRL genotypes were significantly different from each other.

RESULTS: All SNPs were in Hardy-Weinberg equilibrium (Χ2, P≥0.05). rs26311 was the most informative: AA = 49%, AG = 39%, GG = 12%; A = 68%, G = 32%, Heterozigosity = 43% and polymorphism information content = 43%. Running time (h) did not differed (P>0.05) between genotypes (AA = 3.32 ± 0.59; AG = 3.36 ± 0.28; GG = 3.41 ± 0.42, mean ± sd). Homozygotes for the rs26311 A allele had a significantly greater fluid intake (3.0 ± 0.6 L) than heterozygotes (2.1 ± 0.4 L) and G allele homozygotes (1.9 ± 0.4 L). Fluid intake rates (L·h-1) were higher in A allele homozygotes (0.93 ± 0.20 L·h-1) than heterozygote’s (0.61 ± 0.13 L·h-1) and G allele homozygotes (0.56 ± 0.13 L·h-1).

CONCLUSIONS: The present study provides further support to the hypothesis of association between the GHRL gene and fluid intake in long distance runners.

283 Board #135 May 29, 9:30 AM - 11:00 AM

Clinical and Genetic Factors and the Blood Pressure Response to Acute Aerobic Exercise: A Meta-Analysis

Michael L. Bruneau Jr, Tania B. Huedo-Medina, Blair T. Johnson, Kara A. Larson, Linda S. Pescatello, FACSM. University of Connecticut, Storrs-Mansfield, CT.

(No relationships reported)

PURPOSE: We meta-analyzed the literature and found sample features and the angiotensinogen (AGT) M235T (rs699) polymorphism explained 76.9-84.5% and 5.8% of the variability in the BP response to aerobic exercise (AE) training, respectively. This meta-analysis attempted to identify factors explaining variability in the BP response to acute AE.

METHODS: Studies retrieved included: an acute AE intervention and control group; BP before and after AE; and candidate gene polymorphisms. Effect sizes were the standardized mean difference (d) of BP post-vs. pre-exercise vs. control disaggregated by genotype adjusted for baseline sample features. Analyses followed fixed-effects assumptions.

RESULTS: 4 studies from the same trial qualified (N=50). AE interventions were performed at 50.1±10.1% (Mean±SD) maximum oxygen consumption for 40 minsession-1. Participants were men, 44.1±1.0 yr with a BP of 145.7±1.7 / 85.8±0.9 mmHg and body mass index of 29.9±0.3 kgm2. BP responses to acute AE were large and heterogeneous for systolic BP (SBP) (d+= -0.62 [95% CI= 0.75, 0.50], -5.5 mmHg, I2= 48%), and small and homogeneous for diastolic BP (DBP) (d+= -0.28 [95% CI= 0.40, 0.16], -1.7 mmHg, I2= 0%). Clinical sample features explained a large portion of the variability in the SBP response to acute AE (R2= 82.3%, p<0.001); whereas candidate genes explained a marginally significant amount (R2= 4.6%, p= 0.08). Analyses of individual polymorphisms were not feasible due to the low numbers of interventions and observations.

CONCLUSIONS: Clinical sample features explained much of the variability in the BP response to acute AE, while genetic variants had a relatively small contribution. Because all studies derived from a single trial, non-independence is a potential threat. Clinical sample features and genetic factors merit attention in future research examining the inter-individual variability of the BP in response to acute AE among larger, more ethnically diverse samples of men and women.

284 Board #136 May 29, 9:30 AM - 11:00 AM

Influence of MCT1 A1470T Polymorphism on Muscle Injuries Among Elite Italian Soccer Players

Myosotis Massidda1, Carla M. Calò1, Laura Corrias1, Valeria Bachis1, Francesco Piras2, Marco Scorcu2. 1University of Cagliari, Cagliari, Italy. 2Cagliari Calcio Spa and FMSI CR Sardegna, Cagliari, Italy.

(No relationships reported)

Monocarboxylate Transporter 1 (MCT1) mediates the transport of the main fraction of lactate across the sarcolemma. Symptoms and signs of muscle injury on exercise and heat exposure plus subnormal erythrocyte lactate transport have been related with the presence of two mutations in the gene that codifies MCT1.

PURPOSE: We investigated the influence of MCT1 A1470T polymorphism (rs1049434) on indirect muscle injuries rates in top-level soccer players.

METHODS: A sample of 70 elite male soccer players (age 26.5± 4.5 years; stature 181.9±6.6 cm; weight 77.7±6.4 kg) were analyzed during four seasons (form 2009-2010 till 2012-2013). Injury rates (IR) (injuries per 1000 hours of soccer exposure) during seasons as well as prevalence, severity, and type of injuries were considered. The influence of MCT1 A1470T polymorphism on indirect muscle injuries was examined using the one-way ANOVA.

RESULTS: The estimated total incidence was 0.2 indirect muscles injuries per 1000 hours of exposure. The 30 injuries recorded during the four seasons accounted for a loss of 850 days, that is absence from training in the pre-season and regular competitive season.

No significant differences appeared between athletes with different genotypes and injuries rates (p>0.05). However, during the four seasons, we found a trend toward an higher injuries rates in athletes with AA and AT genotypes respect to those with TT genotype (2009-2010 IR; AA=0.16, AT=0.13, TT=0.03; 2010-2011 IR; AA=0.32; AT=0.24; TT=0.02; 2011-2012 IR; AA=0.25; AT=0.06; 2012-2013 IR; AA=2.25; AT=0.69; TT=0.63).

CONCLUSIONS: In our limited sample, the MCT1 A1470T polymorphism did not seem to make a significant contribution to the pathogenesis of indirect muscle injuries in top-level soccer players. However, the trend toward an high injuries rates in athletes with AA and AT genotypes suggests that further future analysis are require to clarify the possible influence of MCT1 polymorphism on muscle injuries in soccer.

285 Board #137 May 29, 9:30 AM - 11:00 AM

Frequency Distribution of ACTN3 in Different Ages in Brazilian Soccer Players

Joao C. Dias1, Daniel B. Coelho2, Eduardo M. Pimenta3, Izinara R. Cruz2, Christiano Veneroso2, Guilherme A. Pussieldi4, Maria Raquel S. Carvalho2, Emerson Silami-Garcia2. 1Centro Universitário de Belo Horizonte, Belo Horizonte, Minas Gerais, Brazil. 2Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. 3Universidad de Leon, Departamento de Ciências Biomédicas, Leon, Spain. 4Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil.

(No relationships reported)

The gene ACTN3 encodes α-actinin-3. A polymorphism in this gene (ACTN3 R577X) alters the expression of α-actinin-3 and was associated to variation in performance in power and speed predominant activities.

PURPOSE: The objective was to identify and compare the different genotype polymorphism ACTN3 frequency in Brazilian soccer players in different categories.

METHODS: The participants were 367 male players. Under 14 (U14) were 14.2±0.3 years old; under 15 (U15) 15.5±0.5; under 17 (U17) 16.3±0.2; under 20 (U20) 18.2±0.4; and professionals (PRO) 22.3±2.5 years old, who were taking part in the main national soccer league in Brazil. The control group was composed of 100 randomly selected subjects in the schools of Belo Horizonte, State of Minas Gerais, where the study was accomplished. The genotyping of the R577X polymorphism in the ACTN3 gene was made by PCR-RFLP using DdeI restriction enzyme and the comparisons were among the different genotype frequencies of ACTN3 namely RR, RX and XX. Genotype frequencies observe for the different soccer player categories tested were compared with X2 tests.

RESULTS: The genotype frequencies observed for ACTN3 in each category were: U14 (RR 58%, RX 30%, XX 12%), U15 (RR 37%, RX 47%, XX 16%), U17 (RR 41%, RX 45%, XX 14%), U20 (RR 43%, RX 43%, XX13%), PRO (RR 43%, RX 52%, XX 13%) e CON (RR 40%, RX 46%, XX 14%).The allele and genotype frequency were in Hardy-Weinberg balance (p=0.442). There was no difference among allele frequencies of different groups. The players and control genotype frequency did not adhere among themselves. The PRO group was lower (0.05%) than all categories (p<0.05) considering XX genotype, as well as the same genotype in comparison with U14(0.12%). Also it was observed an increase of genotype RX in PRO compared with U15.

CONCLUSIONS: Although we did not find significant differences between soccer players and control, it was observed a tendency to a frequency increase in RX genotype and decrease in XX genotype in PRO comparing to all other categories. This found could indicate an artificial selection for mix (power/endurance) characteristic for soccer player subjects.

286 Board #138 May 29, 9:30 AM - 11:00 AM

Variation In The FTO Gene Predicts Exercise Response In The Training Interventions And Genetics Of Exercise Response (TIGER) Study

Matthew P. Herring1, Jose R. Fernandez1, Andrew S. Jackson, FACSM2, Sailors H. Mary3, Daniel P. O’Connor2, Rod K. Dishman, FACSM4, Molly S. Bray1. 1University of Alabama at Birmingham, Birmingham, AL. 2University of Houston, Houston, TX. 3The University of Texas MD Anderson Cancer Center, Houston, TX. 4The University of Georgia, Athens, GA.

(No relationships reported)

PURPOSE: Exercise- and diet-based interventions improve health outcomes, particularly among individuals who adhere to prescribed programs. Responses to exercise training vary widely, even in the highly motivated, suggesting that physiologic factors (e.g., genetic variation) influence exercise response. Thus, this study examined the effect of genetic variation on change in obesity-related outcomes in response to a 15-week vigorous intensity aerobic exercise intervention.

METHODS: Response data from 794 participants (M=302; F=492, 21.3±2.8 y) were analyzed. Factor analysis was performed to create three latent variables, representing body mass/size, fat topography, and blood pressure, used to screen 368 variants in pathways associated with adiposity and metabolism. 119 SNPs (p<.05) were further examined for association to the individual outcome change variables that comprised each latent factor. 85 SNPs in 59 genes were significantly associated with change outcomes. Of these, 13 SNPs in the FTO gene (p<.05) were further analyzed. ANCOVA adjusted for age, gender, and admixture was used to examine the relation of risk-raising alleles and both baseline and change outcomes.

RESULTS: Multiple FTO alleles were significantly associated with change in waist circumference (rs12600060, rs9924072, rs1125392, p<.02) and both baseline WHR (rs7185938, rs12600060, p<.02) and change in WHR (rs9924072, rs1861869, p<.01). Significant genotype by PA interactions were found for change in waist (rs12600060, rs9924072, p<.042) and hip circumferences (rs1861869, p=.041) and WHR (rs12600060, p=.002). When stratified by PA, rs1861869 was significantly associated with change in hip circumference among individuals reporting moderate and high (p=.034), but not low, PA. Rs12600060 and rs1861869 were significantly associated with change in WHR among those reporting high (p<.03), but not moderate or low, PA. Rs12600060 and rs9924072 were significantly associated with change in waist circumference among those reporting low (p<.04), but not moderate or high, PA.

CONCLUSIONS: Variation in the FTO gene may influence exercise response in measures of abdominal obesity and fat topography, both important risk factors for metabolic disease.

287 Board #139 May 29, 9:30 AM - 11:00 AM

Fat Mass and Obesity Associated (FTO) T>A (rs9939609) Genetic Variant Associates with Physical Activity

Harold Lee1, Garrett I. Ash1, Theodore J. Angelopoulos, FACSM2, Priscilla M. Clarkson, FACSM3, Paul M. Gordon, FACSM4, Niall M. Moyna, FACSM5, Paul S. Visich6, Robert F. Zoeller7, Joseph M. Devaney8, Heather Gordish-Dressman8, Paul D. Thompson, FACSM9, Eric P. Hoffman8, Linda S. Pescatello, FACSM1. 1University of Connecticut, Storrs, CT. 2University of Central Florida, Orlando, FL. 3University of Massachusetts, Amherst, MA. 4University of Michigan, Ann Arbor, MI. 5Dublin City University, Dublin, Ireland. 6University of New England, Biddeford, ME. 7Florida Atlantic University, Boca Raton, FL. 8Children’s National Medical Center, Washington, DC. 9Hartford Hospital, Hartford, CT.

(No relationships reported)

Genetic variants in the putative RNA methylase fat mass and obesity associated gene (FTO) are strongly associated with overweight and obesity. Despite the impact of energy expenditure on body weight, the influence of FTO T>A (rs9939609) on habitual physical activity (PA) levels has not been studied.

PURPOSE: We sought to determine whether FTO T>A (rs9939609) associates with habitual PA levels among healthy, European-American adults.

METHODS: Subjects [X±SEM, n=348 (women=196, men=152), 23.6±0.3yr, body mass index (BMI): 24.5±0.3kg·m-2] were genotyped for FTO T>A, and completed the Paffenbarger PA Questionnaire. PA phenotypes were vigorous intensity PA and total PA. Multivariate ANCOVA tested associations among PA phenotypes and genotype by sex and weight status (BMI<25kg·m-2 and ≥25kg·m-2) adjusted for age and BMI. The likelihood-ratio test assessed the % variance attributed to genotype.

RESULTS: Men had higher BMI (p=0.004) but no different age (p≥0.05) than women. FTO T>A interacted with sex and weight status to influence PA (p=0.043). Among men with BMI ≥25kg·m-2, as the number of A alleles increased, more kcal·wk-1 were expended in vigorous intensity PA (TT 353.3±326.8; AT 953.6±295.4; AA 2098.1±546.6) (p=0.027); and total PA (TT 1830.9±462.1; AT 2706.7±417.7; AA 3439.6±772.9), but the latter did not achieve statistical significance (p=0.155). FTO T>A explained 9.8% of the variability in kcal·wk-1 expended in vigorous intensity PA (p=0.006), and 5.8% in total PA (p=0.045). FTO T>A did not associate with vigorous intensity PA or total PA among men with BMI<25kg·m-2, or women regardless of weight status (p≥0.05).

CONCLUSION: Each additional copy of the FTO A allele was associated with an increase of 872.4±157.1kcal·wk-1 expended in vigorous intensity PA and 804.4±41.3kcal·wk-1 expended in total PA among men with overweight. FTO T>A influences the production of the dopamine regulatory enzyme, tyrosine hydroxylase, possibly via RNA demethylation of the genes that affect tyrosine hydroxylase

production. Dopamine is implicated in regulating PA levels and is modulated by estrogen, which may partially explain the FTO T>A and PA associations we observed that were weight and sex dependent.

Supported by NIH-NINDS R01 NS40606-02 and the University of Connecticut Center for Health, Intervention, and Prevention

288 Board #140 May 29, 9:30 AM - 11:00 AM

Alterations in DNA Methylation Associated with Aerobic Exercise Training

Molly S. Bray1, Matthew P. Herring1, Daniel P. O’Connor2, Rodney K. Dishman, FACSM3, Mary H. Sailors4, Andrew S. Jackson, FACSM2. 1University of Alabama at Birmingham, Birmingham, AL. 2University of Houston, Houston, TX. 3University of Georgia, Athens, GA. 4MD Anderson Cancer Center, Houston, TX.

(No relationships reported)

PURPOSE: DNA methylation (MET) is a vital process for regulating gene expression during development and throughout life. While environmental toxins and nutritional alterations are known to influence MET, less is known about how exercise may influence methylation state across the genome. The purpose of this study was to determine how exercise training may alter MET patterns.

METHODS: Illumina HumanMethylation450 BeadChips were used to interrogate whole-genome MET status before and after 15 weeks of aerobic exercise (30 min/day, 3 days/wk). Subjects (n=24) were sedentary at baseline. Differential methylation analysis was followed by ontology/pathway analysis of identified genes.

RESULTS: A total of 3,051 genes were identified as differentially methylated at a p-value of 0.01. After Benajamini-Hochberg correction for multiple testing, 674 genes remained significant. Top networks represented by the unadjusted gene list include cardiovascular system development and function, carbohydrate metabolism, and cellular development and growth. The gene set was most enriched with genes in pathways contributing to autoimmune, signaling, and cancer pathways. Eleven of 14 differentially methylated genes in the type I diabetes pathway are located on chromosome 6 within the Major Histocompatibility Complex, highlighting immune response as a target for exercise-induced alterations in MET.

CONCLUSIONS: Exercise appears to alter methylation at multiple metabolic levels. Our results suggest that exercise induces changes in MET status and may be important in understanding the biology of exercise response.

289 Board #141 May 29, 9:30 AM - 11:00 AM

Pilot Study : DNA Methylation Of Selected Genes Following n-3 Dietary Supplementation

Martin R. Lindley, Nilam Khan, Amarjit Saini, Sarabjit S. Mastana. LoughboroughUniversity, Loughborough, United Kingdom. (Sponsor: T.D. Mickleborough, FACSM)

(No relationships reported)

Methylation of CpG regions along a DNA strand is associated with transcriptional repression. DNA methylation preferentially occurs at the C5 position of cytosine in the context of CG, forming minor bases, 5’-methylcytosines (approx 1% of the genome). Methylated DNA immunoprecipitation microarray (MeDIP) is a genome-wide, high-resolution approach to detect methylation in whole genome or CpG islands levels. Recently there has been much interest in methylation relating to diet and exercise.

PURPOSE: A pilot study to investigate the methylation process that occurs following a bief period of dietary supplementation with n-3 PUFAs (fish oil).

METHODS: DNA was extracted from blood (phenol/chloroform method) pre and post 3 week supplementation(EPA3.2g/DHA2.2g), from one individual. Methylated DNAs were immunoprecipitated via anti-methyl-cytosine antibody. Input and methylated DNA were labelled with fluorescent dyes Cy3 (green) and Cy5 (red), pooled, denatured, and hybridised to a Human DNA Methylation Microarray slide (Agilent G4495A, AMADID 023795 ) containing the annotated human CpG islands and 5000 Undermethylated Regions (UMRs). The slide was scanned (Agilent scanner P/N G2565BA ) and each image was extracted (Agilent feature extraction software v10.5) via Agilent Genomic Workbench 7.0.

RESULTS: Table 1 :Combined Z-score to indicate methylation status pre and post dietary intervention. Negative numbers = de-methylation - positive numbers = methylation.

CONCLUSION: Fish oil supplementation may alter methylation status of a selected number of inflammatory related genes. Gene expression studies are therefore a logical next step towards investigating the mechanism of n-3 derived resolution of inflammation.

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