Abnormal plasma lipids are a major modifiable risk factor for cardiovascular (CV) disease in older persons. Polymorphic variation at numerous gene loci independently and via interactions with environmental factors affect plasma lipid levels. A cross-sectional study and preliminary data suggest that apolipoprotein E (APO E) genotype affects the HDL-C and HDL2-C increases that occur with exercise training. Thus, in healthy, sedentary, middle-aged and older subjects, the investigators will test their primary hypothesis: HDL-C and HDL2-C levels increase more with exercise training in APO E2/3 than in APO E3/4 genotype individuals. Preliminary data also indicate that lipoprotein lipase (LPL) Pvull genotype affects HDL-C and HDL2-C increases resulting from exercise training. Thus, they will test their secondary hypothesis: HDL-C and HDL2-C levels increase more with exercise training in LPL Pvull -/- than in LPL Pvull +/+ or +/- genotype individuals. Exploratory analyses will determine if variations at another LPL and 3 hepatic lipase (HL) gene loci affect the exercise training-induced HDL-C and HDL2-C increases and if, as with preliminary data, LPL and HL activities change differently with exercise training among genotype groups. After screening subjects for APO E genotype, they will be stabilized on an AHA Step I diet. Subjects then complete Baseline Testing, 6 months of exercise training and Final Testing. If VO2max, body composition, or intra-abdominal fat change differently among genotype groups with exercise training, they will be included in linear regression models to assess the independent effects of genetic and non-genetic variables on lipid changes with exercise training. Results consistent with the hypotheses will identify persons who obtain the greatest CV disease risk reductions, resulting in the optimal stratifying of exercise training to those benefiting the most. Conversely, identifying persons who will improve their lipoprotein lipids the least with exercise training would allow them to focus on interventions that might be more efficacious for them.
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