The CAREGENE study: genetic variants of the endothelium and aerobic power in patients with coronary artery disease

Objectives Aerobic phenotypes show a wide variability to similar aerobic training stimuli, which can be partly attributed to heritability. Endothelial function affects aerobic power. Various physiological pathways may influence the endothelial function. Therefore, we aimed to examine whether polymorphisms of the eNos gene, the CAT gene, the VEGF gene, the GPX1gene, the subunit P22 phox of the NAD(P)H-odixase gene, the PPAR-a gene, and the PGC-a gene are associated with aerobic power or with its response to physical training in patients with coronary artery disease (CAD). Methods 935 biologically unrelated Caucasian patients with CAD who had exercised until exhaustion during graded bicycle testing at baseline and after completion of 3 months of training were included in the CAREGENE study (Cardiac Rehabilitation and GENetics of exercise performance). Polymorphisms were detected using the invader assay and MassARRAY technology. Haplotype analysis was performed on the polymorphisms of the eNos gene, the VEGF gene and the NAD(P)H-oxidase gene. Results Physical training significantly increased aerobic power by 24.2 +/- 0.6% (P < 0.001). Associations of P < 0.05 were found between aerobic power and the eNOS 273C>T variant and the catalase -262C>T variant and aerobic power response. Haplotypes of the eNOS polymorhisms were predictive of aerobic power and its response to training (P < 0.05). After Bonferroni correction of multiple testing no significant differences remained. Conclusion We believe that genetic factors are very important in the explanation of the great variability of aerobic power and its response. However, after Bonferroni-correction, differences in these polymorphisms remained no longer statistically significant.