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HIGHLIGHTED TOPICS
Role of Exercise in Reducing the Risk of Diabetes and Obesity
1European University of Madrid, Madrid, Spain; 2Department of Toxicology, Complutense University, Madrid, Spain; 3The Wellcome Trust Sanger Institute, Metabolic Disease Group, Cambridge, United Kingdom; 4Department of Sports Medicine, Higher Sports Council, Madrid, Spain; 5School of Nursing, Complutense University, Madrid, Spain; 6Medical Research Center Epidemiology Unit, Cambridge, United Kingdom; 7The Cooper Institute Center for Human Performance and Nutrition Research, Dallas, Texas; and 8Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona
Submitted 11 January 2005 ; accepted in final form 6 February 2005
Animal and human data indicate a role for the peroxisome proliferator-activated receptor-
coactivator 1
(PPARGC1A) gene product in the development of maximal oxygen uptake (
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 O2 max [73.4 (5.7) vs. 29.4 ml·kg–1·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 
2 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.
single nucleotide polymorphism; maximal oxygen uptake; metabolism; genetics; diabetes
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