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Meta-analyses of the association between the PPARGC1A Gly482Ser polymorphism and athletic performance.

ABSTRACT: Peroxisome proliferator-activated receptor ? coactivator 1? (PGC1?) encoded by the PPARGC1A gene is a vital regulator of glucose and fatty acid oxidation, mitochondrial biogenesis, and skeletal muscle fibre conversion. Several studies have investigated the association between PPARGC1A Gly482Ser polymorphism and athletic performance in humans. However, the results were contradictory. In the present study, two meta-analyses were performed to assess the association between the Gly482Ser polymorphism and endurance or power athletic performance to resolve this inconsistency. Ten articles were identified, including a total of 3,708 athletes and 6,228 controls. Higher frequencies of the Gly/Gly genotype (OR, 1.26; 95% CI, 1.11-1.42) and the Gly allele (OR, 1.29; 95% CI, 1.09-1.52) were observed in Caucasian endurance athletes. Furthermore, higher incidences of the Gly/Gly genotype (OR, 1.30; 95% CI, 1.16-1.46) and the Gly allele (OR, 1.22; 95% CI, 1.12-1.33) were observed in power athletes compared to controls. This finding demonstrates that the Gly/Gly genotype and the Gly allele of the PPARGC1A Gly482Ser polymorphism may facilitate athletic performance regardless of the type of sport, as well as providing solid evidence to support the possible influence of genetic factors on human athletic performance.

SUBMITTER: Chen Y

PROVIDER: S-EPMC6945052 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Meta-analyses of the association between the PPARGC1A Gly482Ser polymorphism and athletic performance.

Chen Ying Y Wang Dongmei D Yan Pingping P Yan Shenglan S Chang Qing Q Cheng Zhi Z

Biology of sport 20191010 4

Peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) encoded by the PPARGC1A gene is a vital regulator of glucose and fatty acid oxidation, mitochondrial biogenesis, and skeletal muscle fibre conversion. Several studies have investigated the association between PPARGC1A Gly482Ser polymorphism and athletic performance in humans. However, the results were contradictory. In the present study, two meta-analyses were performed to assess the association between the Gly482S ...[more]

PMID: 31938000

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Project description:ObjectivesMuscle health is essential for children's physical development and future health. PPARGC1A gene encode the peroxisome proliferator-activated receptor coactivator 1α which coactivates transcription factors that control mediating skeletal muscle fiber type conversion and skeletal muscle fiber formation. The PPARGC1A rs8192678 Gly/Ser (Gly482Ser) polymorphism was associated with the regulation of skeletal muscle fibre type. This paper aims to explore the association between the PPARGC1A rs8192678 (Gly482Ser) polymorphism and muscle fitness in Chinese schoolchildren.MethodsWe detected the distribution of the PPARGC1A rs8192678 (Gly482Ser) polymorphism by DNA typing of saliva samples from untrained Southern Chinese Han children aged 7-12 years. Considering that muscle studies in children cannot use invasive sampling, we analyzed the association between alleles and genotypes with high validity tests of muscle fitness assesment in children(handgrip strength, standing long jump, sit-ups and push-ups).ResultsThe results showed no significant differences in height, weight or body mass index between the sexes. The grip strength indicators were correlated with age in boys and height and weight in girls. Sit-ups were significantly higher in girls with the PPARGC1A Gly/Gly genotype than in boys, and handgrip strength and standing long jump were significantly lower in girls with the PPARGC1A rs8192678 (Gly482Ser) genotype than in boys. Genetic model analysis showed that the Gly482 allele had a dominant genetic effect on the Gly482 allele is hypothesized to influence the expression of type I fibers in skeletal muscle in girls, while the Ser482 allele affects on type II fibers in girls. The two alleles had little genetic effect on boys.ConclusionsThe results suggested the possible association of the PPARGC1A rs8192678 (Gly482Ser) polymorphism on myofibril type-related phenotypes in Han Chinese children in southern China, with a particular impact on girls.

Project description:BACKGROUND:Genetics plays a role in determining potential for athletic ability (AA) and sports performance (SP). In this study, AA involves comparing sedentary controls with competitive athletes in power and endurance activities as well as a mix between the two (SP). However, variable results from genetic association studies warrant a meta-analysis to obtain more precise estimates of the association between PPARGC1A Gly482Ser polymorphism and AA/SP. METHODS:Multi-database literature search yielded 14 articles (16 studies) for inclusion. Pooled odds ratios (ORs) and 95% confidence intervals (CI) were used to estimate associations. Summary effects were modified based on statistical power. Subgroup analysis was based on SP (power, endurance and mixed) and race (Caucasians and Asians). Heterogeneity was assessed with the I2 metric and its sources examined with outlier analysis which dichotomized our findings into pre- (PRO) and post-outlier (PSO). RESULTS:Gly allele effects significantly favoring AA/SP (OR > 1.0, P < 0.05) form the core of our findings in: (i) homogeneous overall effect at the post-modified, PSO level (OR 1.13, 95% CI 1.03-1.25, P = 0.01, I2 = 0%); (ii) initially homogeneous power SP (ORs 1.22-1.25, 95% CI 1.05-1.44, P = 0.003-0.008, I2 = 0%) which precluded outlier treatment; (iii) PRO Caucasian outcomes (ORs 1.29-1.32, 95% CI 1.12-1.54, P = 0.0005) over that of Asians with a pooled null effect (OR 0.99, 95% CI 0.72-1.99, P = 0.53-0.92) and (iv) homogeneous all > 80% (ORs 1.19-1.38, 95% CI 1.05-1.66, P = 0.0007-0.007, I2 = 0%) on account of high statistical power (both study-specific and combined). In contrast, none of the Ser allele effects significantly favored AA/SP and no Ser-Gly genotype outcome favored AA/SP. The core significant outcomes were robust and showed no evidence of publication bias. CONCLUSION:Meta-analytical applications in this study generated evidence that show association between the Gly allele and AA/SP. These were observed in the overall, Caucasians and statistically powered comparisons which exhibited consistent significance, stability, robustness, precision and lack of bias. Our central findings rest on association of the Gly allele with endurance and power, differentially favoring the latter over the former.

Project description:Peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PPARGC1A) regulates the expression of energy metabolism's genes and mitochondrial biogenesis. The essential roles of PPARGC1A encouraged the researchers to assess the relation between metabolism-related diseases and its variants. To study Gly482Ser (+1564G/A) single-nucleotide polymorphism (SNP) after PPARGC1A modeling, we substitute Gly482 for Ser482. Stability prediction tools showed that this substitution decreases the stability of PPARGC1A or has a destabilizing effect on this protein. We then utilized molecular dynamics simulation of both the Gly482Ser variant and wild type of the PPARGC1A protein to analyze the structural changes and to reveal the conformational flexibility of the PPARGC1A protein. We observed loss flexibility in the RMSD plot of the Gly482Ser variant, which was further supported by a decrease in the SASA value in the Gly482Ser variant structure of PPARGC1A and an increase of H-bond with the increase of β-sheet and coil and decrease of turn in the DSSP plot of the Gly482Ser variant. Such alterations may significantly impact the structural conformation of the PPARGC1A protein, and it might also affect its function. It showed that the Gly482Ser variant affects the PPARGC1A structure and makes the backbone less flexible to move. In general, molecular dynamics simulation (MDS) showed more flexibility in the native PPARGC1A structure. Essential dynamics (ED) also revealed that the range of eigenvectors in the conformational space has lower extension of motion in the Gly482Ser variant compared with WT. The Gly482Ser variant also disrupts PPARGC1A interaction. Due to this single-nucleotide polymorphism in PPARGC1A, it became more rigid and might disarray the structural conformation and catalytic function of the protein and might also induce type 2 diabetes mellitus (T2DM), coronary artery disease (CAD), and nonalcoholic fatty liver disease (NAFLD). The results obtained from this study will assist wet lab research in expanding potent treatment on T2DM.

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Meta-analyses of the association between the PPARGC1A Gly482Ser polymorphism and athletic performance.

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Meta-analyses of the association between the <i>PPARGC1A</i> Gly482Ser polymorphism and athletic performance.

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