Is there an association between PPARGC1A genotypes and endurance capacity in Chinese men?
ABSTRACT Our purpose was to determine the possible association between genotypes of three polymorphisms (Gly482Ser, Thr394Thr and A2962G) of the peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A) gene, on one hand, and both the pre- (baseline) and post-training levels of maximal (i.e., maximal oxygen uptake [VO2max]) and submaximal human endurance capacity (i.e., running economy [RE]). We studied 102 young males (physically active, non-athletes; age: 19+/-1 yrs) from Northern China (of Han origin) who underwent a 18-week endurance training (running) program and were tested on a treadmill (for VO2max and RE determination) before and after training. None of the VO2max and RE related traits were associated with the Gly482Ser and Thr394Thr polymorphisms at baseline or after training. The A2962G polymorphism was however associated with VO2max at baseline, as carriers of the G allele (AG+GG genotypes; n=49) had higher levels of VO2max than the AA group (n=53) (58.2+/-4.3 vs 56.3+/-3.9 mL/kg/min; P=0.017). Our results do not support previous data on Caucasians showing an association between the Gly482Ser variant and VO2max but suggest the potential role of another polymorphism (A2962G) to explain individual VO2max differences in Chinese men.
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ABSTRACT: Decreased expression of the peroxisomal proliferator activated receptor gamma coactivator 1 alpha gene (PPARGC1A) is found in patients with type 2 diabetes, and variants in this gene have been linked with type 2 diabetes. Therefore, we investigated the effects of single nucleotide polymorphisms in PPARGC1A on body composition and glucose tolerance and on insulin sensitivity and secretion. Non-diabetic offspring (n=156, age 34.9+/-0.5 years [mean+/-SEM], BMI 26.2+/-0.4 kg/m2) underwent an OGTT and an IVGTT and the hyperinsulinaemic-euglycaemic clamp. The promoter and coding regions of PPARGC1A were sequenced. Two haplotype blocks in PPARGC1A were observed, one in the promoter region (G-1774A, A-1679G, T-1422C, A-1278G, C-543A) and one in the coding region and 3' regions (Thr394Thr, Asp475Asp, Gly482Ser, Thr528Thr, Thr612Met, G+2381A). The coding region haplotype carrying the rare allele in codons 482 and 528 was associated with elevated glucose levels in an OGTT (p=0.024, adjusted for age, sex and BMI) and a haplotype carrying the rare alleles in codons 394 and 475 was associated with low BMI (p=0.033), high rates of whole-body glucose uptake (p=0.045) and low glucose levels in the OGTT (p=0.037). We conclude that PPARGC1A is likely to contribute to the risk of diabetes in offspring of patients with type 2 diabetes.Diabetologia 08/2005; 48(7):1331-4. · 6.49 Impact Factor
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ABSTRACT: Peroxisome proliferator activated receptor gamma coactivator-1 (PGC-1), a transcriptional coactivator of the nuclear receptor PPARgamma, plays a role in adaptive thermogenesis and insulin sensitivity. Plasma fasting insulin has been linked to the chromosomal region where the PGC-1 gene is located. Thus, PGC-1 can be viewed as a functional and positional candidate for the susceptibility gene for Type II (non-insulin-dependent) diabetes mellitus. After screening the PGC-1 gene for single nucleotide polymorphisms (SNPs), we performed an association study using the newly detected SNPs in 537 Type II diabetic patients and 417 non-diabetic subjects. We found three relatively frequent SNPs in the PGC-1 gene (IVS4-11T > C, Thr394Thr and Gly482Ser). There were significant differences in fasting insulin (Gly/Gly; 37.7 +/- 1.43, Gly/Ser; 40.2 +/- 1.21, Ser/Ser; 44.3 +/- 1.82 pmol/l, p = 0.018) and insulin resistance index (Gly/Gly; 1.48 +/- 0.06, Gly/Ser; 1.56 +/- 0.05, Ser/Ser; 1.75 +/- 0.08, p = 0.027) according to the genotype of the Gly482Ser polymorphism. The Thr394Thr - Gly482Ser haplotype was associated with Type II diabetes (p = 0.00003). CONCLUSION/INTERPRETATION. The results of this study suggested that the PGC-1 gene might be implicated in the pathogenesis of Type II diabetes.Diabetologia 05/2002; 45(5):740-3. · 6.49 Impact Factor
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ABSTRACT: Genetic and environmental factors contribute to age-dependent susceptibility to type 2 diabetes. Recent studies have reported reduced expression of PPARgamma coactivator 1alpha (PGC-1alpha) and PGC-1beta genes in skeletal muscle from type 2 diabetic patients, but it is not known whether this is an inherited or acquired defect. To address this question we studied expression of these genes in muscle biopsies obtained from young and elderly dizygotic and monozygotic twins without known diabetes before and after insulin stimulation and related the expression to a Gly482Ser variant in the PGC-1alpha gene. Insulin increased and aging reduced skeletal muscle PGC-1alpha and PGC-1beta mRNA levels. This age-dependent decrease in muscle gene expression was partially heritable and influenced by the PGC-1alpha Gly482Ser polymorphism. In addition, sex, birth weight, and aerobic capacity influenced expression of PGC-1alpha in a complex fashion. Whereas expression of PGC-1alpha in muscle was positively related to insulin-stimulated glucose uptake and oxidation, PGC-1beta expression was positively related to fat oxidation and nonoxidative glucose metabolism. We conclude that skeletal muscle PGC-1alpha and PGC-1beta expression are stimulated by insulin and reduced by aging. The data also suggest different regulatory functions for PGC-1alpha and PGC-1beta on glucose and fat oxidation in muscle cells. The finding that the age-dependent decrease in the expression of these key genes regulating oxidative phosphorylation is under genetic control could provide an explanation by which an environmental trigger (age) modifies genetic susceptibility to type 2 diabetes.Journal of Clinical Investigation 12/2004; 114(10):1518-26. · 12.81 Impact Factor