INTERACTIVE EFFECTS OF ENOS T-786C GENE POLYMORPHISM AND CARDIOVASCULAR FITNESS ON FLOW-MEDIATED DILATION IN FEMALES

Abstract

In vitro studies have shown that a T→-786C variant in the promoter region of the endothelial nitric oxide synthase (eNOS) gene suppresses eNOS transcription, which may affect vascular responses and lead to cardiovascular (CV) disease. PURPOSE To determine whether the eNOS T-786C gene polymorphism interacted with CV fitness level to associate with flow-mediated dilation (FMD). METHODS Venous occlusion plethysmography was used to measure forearm blood flow (FBF) response during 3 min of reactive hyperemia (RH) following 5 min of ischemia in sedentary (SED) (n=28) and endurance trained (TR) (n=35) Caucasian females (25±1 yr). eNOS T-786C genotype was determined by PCR. CV fitness levels were determined by a VO2max test. Body fat percentage (%BF) was determined by skinfold measurements. RESULTS The C allele carriers (TC+CC, n=31) were compared with the TT homozygotes (n=31). VO2max was greater (33.8±1 vs 45.3±1 ml/kg/min, P < 0.001) and %BF was lower (26.3±1% vs 19.3±1%, P < 0.001) in TR compared to SED subjects. VO2max (40.1±1 vs 40.3±1 ml/kg/min) and %BF (22.4±1% vs 22.3±1%) were not significantly different between TT and TC+CC genotype groups. There was a significant interaction between eNOS T-786C genotype and CV fitness level on the percent change in FBF (%ΔFBF) throughout the 3 min of RH (P=0.02). In the TC+CC genotype group %ΔFBF was greater in the TR subjects, while in the TT genotype group, %ΔFBF was greater in SED than in TR subjects. The TC+CC genotype group had a significantly lower %ΔFBF compared to the TT genotype group at 1 min (peak FBF) of RH (139±18% vs 190±19%, P=0.04). Repeated measures ANOVA demonstrated that across the 3 min of RH, %ΔFBF was significantly greater in the TT compared to the TC+CC genotype group (P=0.03). CONCLUSION The C allele of the eNOS T-786C gene polymorphism appears to be associated with an attenuated FMD response, however it appears that individuals with a C allele improve their vascular function the most with endurance training.