High-density lipoprotein-cholesterol, its subfractions, and responses to exercise training are dependent on endothelial lipase genotype

Plasma high-density lipoprotein cholesterol (HDL-C) levels are an important independent risk factor for cardiovascular disease (CVD) that can be modified through exercise training. However, levels of HDL-C and its subfractions and their response to standardized exercise training are highly variable among individuals. Such variability suggests that levels of HDL-C, its subfractions, and their response to exercise training may be influenced by genetic variation and the interaction of that genetic variation with physical activity. The endothelial lipase gene (LIPG) may influence HDL-C metabolism and has several recently identified genetic variants. We hypothesized that the LIPG Thr111Ile polymorphism would be associated with variation in HDL-C levels and its subfractions and their response to exercise training. Eighty-three sedentary, healthy 50- to 75-year-old subjects were weight-maintained on an American Heart Association Step 1 Diet and then studied before and after aerobic exercise training. Sample size varied according to outcome measure as complete data was not available for all subjects. Initial age, body composition, and maximum oxygen consumption (Vo_2max) did not differ between LIPG genotype groups (CC, n = 41 to 44; CT/TT, n = 37 to 39). Initial total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels were not significantly different between groups. The CT/TT group had lower initial HDL_2NMR-C (12 plusmn; 1.0 v 17 ± 1.1 mg/dL; P = .002) and integrated HDL_1,2NMR-C (13 ± 1.0 v 18 ± 1.1 mg/dL; P = .002) levels and somewhat higher initial levels of integrated HDL_3,4,5-C (31 ± 2.2 v 25 ± 2.3 mg/dL; P = .06). With exercise training, Vo_2max increased, and body weight, total body fat, and visceral adipose tissue decreased similarly in both groups. With training, HDL-C levels increased twice as much (4.4 ± 0.8 v 1.9 ± 0.9 mg/dL; P = .04), HDL₃-C levels increased almost 2-fold greater (3.8 ± 0.7 v 2.2 ± 0.6 mg/dL; P = .07), and HDL_5NMR-C levels increased more than 4 times as much (2.2 ± 0.8 v 0.5 ± 0.6 mg/dL; P = .08) in the CC compared to the CT/TT group. We conclude that the LIPG genotype is associated with interindividual variability in HDL-C and its subfractions and their response to exercise training.