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FRANKS, P. W., I. BARROSO, J. LUAN, U. EKELUND, V. E. F. CROWLEY, S. BRAGE, M. S. SANDHU, R. W. JAKES, R. P. S. MIDDELBERG, A.-H. HARDING, A. J. SCHAFER, S. O'RAHILLY, and N. J. WAREHAM. PGC-1[alpha] Genotype Modifies the Association of Volitional Energy Expenditure with [latin capital V with dot above]O2max. Med. Sci. Sports Exerc., Vol. 35, No. 12, pp. 1998-2004, 2003. Sedentary lifestyles are increasingly common and result in low cardiorespiratory fitness ([latin capital V with dot above]O2max), a well-established predictor of early mortality and coronary heart disease (CHD). Adaptation in [latin capital V with dot above]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-1[alpha]) coactivates genes involved in energy transduction and mitochondrial biogenesis. Transgenic mouse data demonstrate that overexpression of PGC-1[alpha] mRNA increases endurance capacity by transformation of nonoxidative to oxidative skeletal muscle tissue. Other murine studies demonstrate that exercise increases PGC-1[alpha] mRNA expression.

Purpose: To explore whether a candidate polymorphism in the PGC-1[alpha] gene modifies the association between physical activity energy expenditure (PAEE) and predicted [latin capital V with dot above]O2max ([latin capital V with dot above]O2max.pred).

Method: We examined whether the Gly482Ser polymorphism of PGC-1[alpha] modified the relationship between objectively measured PAEE and [latin capital V with dot above]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. [latin capital V with dot above]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 [latin capital V with dot above]O2max.pred (mL[middle dot]kg-1[middle dot]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 [latin capital V with dot above]O2max.pred (L[middle dot]min-1) was highly significant (P = 0.009).

Conclusion: 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.

(C)2003The American College of Sports Medicine