title: Hepatic lipase gene -514C>T variant is associated with exercise training-induced changes in VLDL and HDL by lipoprotein lipase.
abstract: Our objective was to test the hypothesis that a common polymorphism in the hepatic lipase (HL) gene (LIPC -514C>T, rs1800588) influences aerobic exercise training-induced changes in TG, very-low-density lipoprotein (VLDL), and high-density lipoprotein (HDL) through genotype-specific increases in lipoprotein lipase (LPL) activity and that sex may affect these responses. Seventy-six sedentary overweight to obese men and women aged 50-75 yr at risk for coronary heart disease (CHD) underwent a 24-wk prospective study of the LIPC -514 genotype-specific effects of exercise training on lipoproteins measured enzymatically and by nuclear magnetic resonance, postheparin LPL and HL activities, body composition by dual energy x-ray absorptiometry and computer tomography scan, and aerobic capacity. CT genotype subjects had higher baseline total cholesterol, HDL-C, HDL(2)-C, large HDL, HDL particle size, and large LDL than CC homozygotes. Exercise training elicited genotype-specific decreases in VLDL-TG (-22 vs. +7%; P < 0.05; CC vs. CT, respectively), total VLDL and medium VLDL, and increases in HDL-C (7 vs. 4%; P < 0.03) and HDL(3)-C with significant genotype×sex interactions for the changes in HDL-C and HDL(3)-C (P values = 0.01-0.02). There were also genotype-specific changes in LPL (+23 vs. -6%; P < 0.05) and HL (+7 vs. -24%; P < 0.01) activities, with LPL increasing only in CC subjects (P < 0.006) and HL decreasing only in CT subjects (P < 0.007). Reductions in TG, VLDL-TG, large VLDL, and medium VLDL and increases in HDL(3)-C and small HDL particles correlated significantly with changes in LPL, but not HL, activity only in CC subjects. This suggests that the LIPC -514C>T variant significantly affects training-induced anti-atherogenic changes in VLDL-TG, VLDL particles, and HDL through an association with increased LPL activity in CC subjects, which could guide therapeutic strategies to reduce CHD risk.
authors.affiliation: Dept. of Kinesiology, Univ. of Maryland, College Park, MD 20742-2611, USA.
authors.forename: Tina E
authors.initials: TE
authors.lastname: Brinkley
authors.forename: Amy
authors.initials: A
authors.lastname: Halverstadt
authors.forename: Dana A
authors.initials: DA
authors.lastname: Phares
authors.forename: Robert E
authors.initials: RE
authors.lastname: Ferrell
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Prigeon
authors.forename: James M
authors.initials: JM
authors.lastname: Hagberg
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Goldberg
mesh_terms: D000368:Aged; D001483:Base Sequence; D003327:Coronary Disease / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D017931:DNA Primers / Q000235:genetics; D005081:Exercise Therapy; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000097:blood*; D008079:Lipoproteins, VLDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors; D057185:Sedentary Behavior; D014280:Triglycerides / Q000097:blood
chemical_list: D017931:DNA Primers; C504173:LIPC protein, human; D008075:Lipoproteins, HDL; D008079:Lipoproteins, VLDL; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride; D008049:Lipase; C548261:LPL protein, human; D008071:Lipoprotein Lipase