title: PPARGC1A genotype (Gly482Ser) predicts exceptional endurance capacity in European men.
abstract: Animal and human data indicate a role for the peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PPARGC1A) gene product in the development of maximal oxygen uptake (V(O2 max)), a determinant of endurance capacity, diabetes, and early death. We tested the hypothesis that the frequency of the minor Ser482 allele at the PPARGC1A locus is lower in World-class Spanish male endurance athletes (cases) [n = 104; mean (SD) age: 26.8 (3.8) yr] than in unfit United Kingdom (UK) Caucasian male controls [n = 100; mean (SD) age: 49.3 (8.1) yr]. In cases and controls, the Gly482Ser genotype met Hardy-Weinberg expectations (P > 0.05 in both groups tested separately). Cases had significantly higher V(O2 max) [73.4 (5.7) vs. 29.4 ml x kg(-1) x min(-1) (3.8); P < 0.0001] and were leaner [body mass index: 20.6 (1.5) vs. 27.6 kg/m2 (3.9); P < 0.0001] than controls. In unadjusted chi2 analyses, the frequency of the minor Ser482 allele was significantly lower in cases than in controls (29.1 vs. 40.0%; P = 0.01). To assess the possibility that genetic stratification could confound these observations, we also compared Gly482Ser genotype frequencies in Spanish (n = 164) and UK Caucasian men (n = 381) who were unselected for their level of fitness. In these analyses, Ser482 allele frequencies were very similar (36.9% in Spanish vs. 37.5% in UK Caucasians, P = 0.83), suggesting that confounding by genetic stratification is unlikely to explain the association between Gly482Ser genotype and endurance capacity. In summary, our data indicate a role for the Gly482Ser genotype in determining aerobic fitness. This finding has relevance from the perspective of physical performance, but it may also be informative for the targeted prevention of diseases associated with low fitness such as Type 2 diabetes.
authors.affiliation: European University of Madrid, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Lucia
authors.forename: Félix
authors.initials: F
authors.lastname: Gómez-Gallego
authors.forename: Inês
authors.initials: I
authors.lastname: Barroso
authors.forename: Manuel
authors.initials: M
authors.lastname: Rabadán
authors.forename: Fernando
authors.initials: F
authors.lastname: Bandrés
authors.forename: Alejandro F
authors.initials: AF
authors.lastname: San Juan
authors.forename: José L
authors.initials: JL
authors.lastname: Chicharro
authors.forename: Ulf
authors.initials: U
authors.lastname: Ekelund
authors.forename: Soren
authors.initials: S
authors.lastname: Brage
authors.forename: Conrad P
authors.initials: CP
authors.lastname: Earnest
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Wareham
authors.forename: Paul W
authors.initials: PW
authors.lastname: Franks
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004252:DNA Mutational Analysis; D005060:Europe / Q000453:epidemiology; D015444:Exercise / Q000502:physiology*; D017079:Exercise Tolerance / Q000235:genetics*; D005838:Genotype; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008297:Male; D010101:Oxygen Consumption / Q000235:genetics*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010807:Physical Endurance / Q000235:genetics; D010809:Physical Fitness / Q000502:physiology*; D015995:Prevalence; D013030:Spain / Q000453:epidemiology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D006360:Heat-Shock Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors