PPARGC1A genotype (Gly482Ser) predicts exceptional endurance capacity in European men

Complutense University of Madrid, Madrid, Madrid, Spain
Journal of Applied Physiology (Impact Factor: 3.06). 08/2005; 99(1):344-8. DOI: 10.1152/japplphysiol.00037.2005
Source: PubMed


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.

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    • "re could affect mRNA expression and/or protein levels (Eynon et al. 2010). Moreover, the PPARGC1A 482Ser allele was associated with type 2 diabetes (Ek et al. 2001;Hara et al. 2002), and the individuals with 482 Gly allele had beneficial effects on the alteration of lipid oxidation and early insulin secretion (Muller et al. 2003;Eynon et al. 2010).Lucia et al. (2005)also reported an association between elite athletic performance and PPARGC1A gene variants in which the deficit of the PPARGC1A 482Ser allele in elite endurance athletes was observed. However, opposing results to these positive associations have also been published. For example, there were no significant associations found between maxima"
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    ABSTRACT: The peroxisome proliferator-activated receptor δ (PPARD) and peroxisome proliferator-activated receptor γ coactivator 1α (PPARGC1A) genes recently have been suggested to have an association with athletic performance and physical endurance. These gene products are reported to be crucial components in training-induced muscle adaptation, since they are related with mRNA and/or protein activity in coordinated response to exercise. To assess the possible contribution of the PPARD T294C/PPARGC1A Gly482Ser polymorphism to differences in physical endurance, we performed a population-based study of 111 Korean athletes and 145 healthy controls based on their genotype distribution of the genes. The two loci were found to be not deviated from Hardy–Weinberg equilibrium. There were no differences in genotype distribution of PPARD T294C and PPARGC1A Gly482Ser between the athletic group and controls (p > 0.05). In contrast, we found a significant association between the PPARGC1A Gly482Ser polymorphism and the 20 m shuttle run activity (a measure of endurance performance) in the athletic group (p = 0.003). The result showed a remarkable increase in the numbers of shuttle run ratio from subjects with the PPARGC1A Gly/Gly genotype (85.29 ± 28.80) than those with the Gly/Ser (58.05 ± 32.76) and Ser/Ser (68.38 ± 30.47) genotypes. Thus, our data imply that the PPARGC1A Gly/Gly genotype may provide a beneficial effect on elite-level endurance status, although functional studies with larger sample sizes are necessary to elucidate these findings.
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    • "From the present results it is likely that it is this deficiency in exercise-induced fast-to-slow fibre type transformation which explains the reduced aerobic performance level of persons with the Gly482Ser SNP[35,33,30,363738. The impaired MEF2 binding to PGC-1α may then also explain the observation that carriers of the Gly482Ser SNP exhibit a reduced insulin sensi- tivity[33,34]and a higher risk for metabolic syndrome and type 2 diabetes[35,33,30,36,37]. This because MEF2 is required for the muscle-specific expression of the insulin-responsive glucose transporter 4 (GLUT4)[75,76]. "
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    ABSTRACT: PGC-1α (peroxisome proliferator-activated receptor γ co-activator 1α) is an important regulator of mitochondrial biogenesis and a master regulator of enzymes involved in oxidative phosphorylation. Recent evidence demonstrated that the Gly482Ser single nucleotide polymorphism (SNP) in the PGC-1α gene affects insulin sensitivity, blood lipid metabolism and binding to myocyte enhancer factor 2 (MEF2). Individuals carrying this SNP were shown to have a reduced cardiorespiratory fitness and a higher risk to develop type 2 diabetes. Here, we investigated the responses of untrained men with the Gly482Ser SNP to a 10 week programme of endurance training (cycling, 3 x 60 min/week, heart rate at 70-90% VO2peak). Quantitative data from analysis of biopsies from vastus lateralis muscle revealed that the SNP group, in contrast to the control group, lacked a training-induced increase in content of slow contracting oxidative fibres. Capillary supply, mitochondrial density, mitochondrial enzyme activities and intramyocellular lipid content increased similarly in both groups. These results indicate that the impaired binding of MEF2 to PGC-1α in humans with this SNP impedes exercise-induced fast-to-slow muscle fibre transformation.
    Full-text · Article · Apr 2015 · PLoS ONE
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    • "Moreover, results suggest that the mitochondrial function associated with aerobic fitness and insulin resistance is deeply affected by the expression of coactivators (PGC-1í µí»¼ and PGC- 1í µí»½) of the PPARG [13]. Therefore, PPARG may be a promising candidate for regulation by maximal oxygen uptake [14]. The cardiorespiratory fitness as defined by maximal oxygen uptake (VO 2 max) is modulated largely by physical activity level and genotype. "
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    ABSTRACT: The influence of cardiorespiratory fitness (VO 2 max) on anthropometric variables and PPARG mRNA expression was investigated. Monozygotic twin pairs aged 11–18 years were grouped into discordant (D) and concordant (C) high and low VO 2 max groups. VO 2 max was determined by progressive maximal exercise test on treadmill with gas exchange analysis. Body mass (BM), BMI, waist circumference (WC), triceps (TR), and subscapular (SB) skinfold thicknesses were measured. Twins from the discordant group had differences in VO 2 max values (D-high = 45.9 ± 10.0 versus D-low = 32.4 ± 10.6 mL⋅kg −1 ⋅min −1 , í µí±ƒ = 0.025), while no differences were found in the concordant group (C-high = 42.4 ± 9.2 versus C-low = 38.8 ± 9.8 mL⋅kg −1 ⋅min −1 , í µí±ƒ = 0.952). In discordant group, VO 2 max was negatively correlated with TR + SB (í µí±Ÿ = −0.540, í µí±ƒ = 0.021) and positively correlated with PPARG expression in leukocytes (í µí±Ÿ = 0.952, í µí±ƒ = 0.001). Moreover, PPARG expression was directly correlated with BM (í µí±Ÿ = 0.714, í µí±ƒ = 0.047) and height (í µí±Ÿ = 0.762, í µí±ƒ = 0.028). In concordant twins, VO 2 max was inversely correlated with BM (í µí±Ÿ = −0.290, í µí±ƒ = 0.027), BMI (í µí±Ÿ = −0.472, í µí±ƒ = 0.001), WC (í µí±Ÿ = −0.426, í µí±ƒ = 0.001), and TR + SB (í µí±Ÿ = −0.739, í µí±ƒ = 0.001). Twins D-high had 1.78-fold greater PPARG expression when compared with twins D-low (í µí±ƒ = 0.048). In conclusion, the cardiorespiratory fitness may modulate PPARG expression in childhood and adolescence, independently of the genetic background.
    Full-text · Article · Apr 2015 · Journal of Diabetes Research
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