The skeletal muscle-specific isoform of adenosine monophosphate deaminase (AMPD) is one of the most important regulators of muscle energy metabolism. A nonsense C to T transition in nucleotide 34 (C34T) in exon 2 of AMPD1 gene converts the codon CAA into the premature stop-codon TAA. 127 Polish male rowers including Olympic and world champions were recruited for this study. Controls samples were obtained from 251 unrelated volunteers. Statistically significant differences in genotype distribution were observed when only a whole group of rowers (88.19% CC, 11.81% CT, 0% TT; p=0.009) were compared with controls (75.31% CC, 23.10% CT, 1,59% TT). A significant deficiency of the T allele compared to control samples was noted in the elite rowers (4.55%, p=0.021) and non-elite rowers (6.63%, p=0.023), whereas this trend was even stronger when compared with the controls for the whole group of rowers (5.91%, p=0.002). Our results suggest that the T allele is associated with physical performance level, therefore, it may be included in the group of performance altering polymorphisms as a negative factor to athletic performance.

Cardiorespiratory responses to exercise and the c34t ampd1 gene polymorphism in the heritage family study

Is the C34T Polymorphism of the AMPD1 Gene Associated with Athlete Performance in Rowing

Despite the use of current therapies for lipid modification, glucose regulation, and blood pressure control, residual cardiovascular risk persists, creating a need for additional treatment modalities. The endothelium is essential for the regulation of vascular tone and the maintenance of vascular homeostasis. Endothelial dysfunction is instrumental in the pathogenesis of vascular disease, and independently predicts cardiovascular risk. The endothelium is thus an important treatment target in addition to traditional cardiovascular risk factors. 

This thesis describes a series of clinical studies that were designed to address further strategies for cardiovascular risk reduction. Coenzyme Q10 is an obligatory cofactor in the mitochondrial electron transport chain and a lipophilic antioxidant that may have a complementary role in modifying cardiovascular risk. Statins have well proven benefits on endothelial function and cardiovascular risk reduction, but are yet to be established for non-ischemic heart failure. In parallel, strategies are required to improve statin tolerance and thus cardiovascular risk management.

In the first study, 12 weeks of coenzyme Q10 supplementation resulted in significantly improved endothelial function in statin-treated patients with the metabolic syndrome. In the second study, 12 weeks of coenzyme Q10 therapy did not lead to clinically significant reductions in systolic or diastolic 24-hr ambulatory blood pressure in patients with the metabolic syndrome and inadequately treated hypertension, despite standard therapies; but there was a significant reduction in daytime diastolic blood pressure loads. In the third study, 12 weeks of supplementation with coenzyme Q10 in combination with upward titration of simvastatin therapy from 10 mg/day to 40 mg/day was not associated with improved simvastatin tolerability, nor reduced muscle symptoms in patients with a history of statin-related myalgia compared to statin monotherapy. In the fourth study, genetic variation of COQ2 and AMPD1 were found to be associated with the risk of statin-induced myopathy in two independent cohorts of cases with a history of statin-induced myopathy and statin tolerant controls. A significant gene interaction was observed between COQ2 SNP-2 and AMPD1 Q12X, highlighting an increased risk of statin myopathy with affected alleles. The fifth study, demonstrated that chronic high-term, long-high statin therapy does not lead to subnormal plasma coenzyme Q10 concentrations in patients with phenotypic or genotypic familial hypercholesterolemia compared to untreated controls, although low coenzyme Q10 levels were associated with increased arterial stiffness in patients with familial hypercholesterolemia. In the final study, short-term treatment with atorvastatin resulted in marked improvements in endothelial function in patients with non-ischemic heart failure that were largely independent of LDL-cholesterol reductions. This was not mediated via reductions in plasma asymmetric dimethylarginine levels.

Coenzyme Q10…

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Cardiorespiratory responses to exercise and the c34t ampd1 gene polymorphism in the heritage family study

Citations

Is the C34T Polymorphism of the AMPD1 Gene Associated with Athlete Performance in Rowing

Metabolic Regulation of Endothelial Dysfunction and Cardiovascular Risk

References

Is the C34T Polymorphism of the AMPD1 Gene Associated with Athlete Performance in Rowing

Metabolic Regulation of Endothelial Dysfunction and Cardiovascular Risk

Related Papers (2)

Association of a common variant in the AMPD1 gene with exercise capacity in patients with heart failure: prelude to a positive prognosis?

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