title: PGC-1alpha genotype modifies the association of volitional energy expenditure with [OV0312]O2max.
abstract: Sedentary lifestyles are increasingly common and result in low cardiorespiratory fitness ([OV0312]O2max), a well-established predictor of early mortality and coronary heart disease (CHD). Adaptation in [OV0312]O2max after exercise training varies considerably between people. Because there are hereditary components to fitness, it is likely that genetic factors explain some of this variability. PPARGC1 (PGC-1alpha) coactivates genes involved in energy transduction and mitochondrial biogenesis. Transgenic mouse data demonstrate that overexpression of PGC-1alpha mRNA increases endurance capacity by transformation of nonoxidative to oxidative skeletal muscle tissue. Other murine studies demonstrate that exercise increases PGC-1alpha mRNA expression.
  
  
  OBJECTIVE
  To explore whether a candidate polymorphism in the PGC-1alpha gene modifies the association between physical activity energy expenditure (PAEE) and predicted [OV0312]O2max ([OV0312]O2max.pred).
  
  
  METHODS
  We examined whether the Gly482Ser polymorphism of PGC-1alpha modified the relationship between objectively measured PAEE and [OV0312]O2max.pred in a population-based sample of 599 healthy middle-aged people. PAEE was assessed using individual calibration with 4 d of heart rate monitoring. [OV0312]O2max.pred was measured during a submaximal exercise stress test on a bicycle ergometer.
  
  
  RESULTS
  Homozygosity at the Ser482 allele was found in 12.7% of the cohort, whereas 38.9% and 48.4% carried the Gly482Gly and Gly482Ser genotypes, respectively. The association between PAEE and [OV0312]O2max.pred (mL x kg(-1) x min(-1)) was strongest in people homozygous for the Ser482 allele (beta = 12.03; P < 0.00001) compared with carriers of the Gly allele (beta = 5.61; P < 0.00001). In a recessive model for the Ser482 allele, the interaction between PAEE and genotype on [OV0312]O2max.pred (L x min(-1)) was highly significant (P = 0.009).
  
  
  CONCLUSIONS
  Our results indicate that Ser482 homozygotes may be most capable of improving cardiorespiratory fitness when physically active, and that Gly482Ser may explain some of the between-person variance previously reported in cardiorespiratory adaptation after exercise training.
authors.affiliation: Institute of Public Health, University of Cambridge, United Kingdom.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Franks
authors.forename: Inês
authors.initials: I
authors.lastname: Barroso
authors.forename: Jian'an
authors.initials: J
authors.lastname: Luan
authors.forename: Ulf
authors.initials: U
authors.lastname: Ekelund
authors.forename: Vivion E F
authors.initials: VE
authors.lastname: Crowley
authors.forename: Søren
authors.initials: S
authors.lastname: Brage
authors.forename: Manjinder S
authors.initials: MS
authors.lastname: Sandhu
authors.forename: Rupert W
authors.initials: RW
authors.lastname: Jakes
authors.forename: Rita P S
authors.initials: RP
authors.lastname: Middelberg
authors.forename: Anne-Helen
authors.initials: AH
authors.lastname: Harding
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Schafer
authors.forename: Stephen
authors.initials: S
authors.lastname: O'Rahilly
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Wareham
mesh_terms: D000328:Adult; D000368:Aged; D004734:Energy Metabolism / Q000235:genetics*; D015444:Exercise / Q000502:physiology*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption / Q000235:genetics*; D010809:Physical Fitness / Q000502:physiology; D011110:Polymorphism, Genetic; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D015534:Trans-Activators; D014157:Transcription Factors; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1