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

European University of Madrid, Spain.
Journal of Applied Physiology (Impact Factor: 3.43). 08/2005; 99(1):344-8. DOI: 10.1152/japplphysiol.00037.2005
Source: PubMed

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.

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    ABSTRACT: Ring-Dimiriou S, Kedenko L, Kedenko I, Feichtinger RG, Steinbacher P, Stoiber W, Foerster H, Felder T, Mueller E, Kofler B, Paulweber B. Does Genetic Variation in PPARGC1A Affect Exercise-Induced Changes in Ventilatory Thresholds and Metabolic Syndrome? JEPonline 2014;17(2):1-18. It has been demonstrated that single nucleotide polymorphism (SNP) in the peroxisome proliferator-activated receptor- coactivator-1 gene (PPARGC1A, rs8192678, G/A) affect the exercise-induced change in maximal oxygen uptake (VO2). However, studies investigating the effect of this SNP on submaximal exercise performance markers are quite sparse. Therefore, we investigated the effect of a 10-wk supervised cycling training (3x 60 min•wk-1) on VO2 and work rate at the point of optimal ventilatory efficiency (POE), anaerobic threshold (ANT), respiratory compensation point (RCP), and maximum level in subjects with different genotypes in PPARGC1A. Analyses were completed in 24 untrained men aged 58 ± 6 yrs. Regarding genotype (G/A; Gly482Ser), three groups were formed (3x n=8): GT1 (G/G, wild type, common allele frequency); GT2 (A/A, homozygous); and GT3 (G/A, heterozygous). Before and after the exercise intervention blood samples and body composition in the fasted state were tested, and an incremental cycle ergometer test (10 W•min-1) until volitional exhaustion with measurements of respiratory gas exchange and heart rate were completed. In sum, the occurrence rate of metabolic syndrome was not affected by genotype or short-term supervised cycling. Ten weeks of cycling at 80-100% ANT and 90-120% RCP improved VO2 and work rate at POE and RCP significantly. Furthermore, repeated ANOVA revealed a significant interaction between genotype and exercise with the highest responder in GT1 compared to GT3 and GT2. The results of this prospective study point towards the hypothesis that the SNP rs8192678 affects the trainability of aerobic capacity measured as VO2 or work rate at RCP of previously untrained middle-aged men. Key Words: PPARGC1A, Exercise-Induced Trainability, Untrained Adults
    JEPonline. 04/2014; 17(2):1-18.
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    ABSTRACT: The aim of this study was to investigate the effect of PPAR-α intron 7G>C and PPARGC1A gene Gly482Ser polymorphisms on aerobic performance of elite level endurance athletes. This study was carried out on 170 inviduals (60 elite level endurance athletes and 110 sedentary controls). Aerobic performance of athletes and sedentary control groups were defined by maximal oxygen uptake capacity. DNA was isolated from peripheral blood using GeneJet Genomic DNA Purification kit. Genotyping of the PPAR-α intron 7G>C and PPARGC1A Gly482Ser polymorphisms was performed using PCR-RFLP methods, and statistical evaluations were carried out using SPSS 15.0. Mean age of athletes were 21.38 ± 2.83 (18-29) and control mean age were 25.92 ± 4.88 (18-35). Mean maximal oxygen consumption of athletes were 42.14 ± 7.6 ml/(kg min) and controls were 34.33 ± 5.43 ml/(kg min). We found statistically significant differences between the athlete and control groups with respect to both PPAR-α and PPARGC1A genotype distributions (p = 0.006, <0.001, respectively) and allele frequencies (<0.001, <0.001, respectively). Additionally, when we examined PPAR-α and PPARGC1A genotype distributions according to the aerobic performance test parameters, we found a statistically significant association between velocity, time and maximal oxygen consumption and PPAR-α and PPARGC1A genotypes (p < 0.001). To our knowledge, this is the first study in Turkey examined PPAR-α intron 7G>C and PPARGC1A Gly482Ser gene polymorphisms in elite level endurance athletes. Our results suggest that PPAR-α and PPARGC1A genes have strong effect on aerobic performance of elit level athletes.
    Molecular Biology Reports 07/2014; · 1.96 Impact Factor
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    ABSTRACT: Aims/hypothesis PPARGC1A and PPARGCB encode transcriptional coactivators that regulate numerous metabolic processes. We tested associations and treatment (i.e. metformin or lifestyle modification) interactions with metabolic traits in the Diabetes Prevention Program, a randomised controlled trial in persons at high risk of type 2 diabetes. Methods We used Tagger software to select 75 PPARGCA1 and 94 PPARGC1B tag single-nucleotide polymorphisms (SNPs) for analysis. These SNPs were tested for associations with relevant cardiometabolic quantitative traits using generalised linear models. Aggregate genetic effects were tested using the sequence kernel association test. Results In aggregate, PPARGC1A variation was strongly associated with baseline triacylglycerol concentrations (p = 2.9 × 10−30), BMI (p = 2.0 × 10−5) and visceral adiposity (p = 1.9 × 10−4), as well as with changes in triacylglycerol concentrations (p = 1.7 × 10−5) and BMI (p = 9.9 × 10−5) from baseline to 1 year. PPARGC1B variation was only associated with baseline subcutaneous adiposity (p = 0.01). In individual SNP analyses, Gly482Ser (rs8192678, PPARGC1A) was associated with accumulation of subcutaneous adiposity and worsening insulin resistance at 1 year (both p < 0.05), while rs2970852 (PPARGC1A) modified the effects of metformin on triacylglycerol levels (p interaction = 0.04). Conclusions/interpretation These findings provide several novel and other confirmatory insights into the role of PPARGC1A variation with respect to diabetes-related metabolic traits. Trial registration NCT00004992
    Diabetologia 03/2014; 57(3). · 6.88 Impact Factor