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Hepatic Lipase Gene Variant –514C>T Is Associated With Lipoprotein and Insulin Sensitivity Response to Regular Exercise

The HERITAGE Family Study

¹ Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana
² Department of Pediatrics, "F. Fede" Second University of Naples, Napoli, Italy
³ Lipid Research Center, CHUL Medical Research Center, Québec, Canada
⁴ Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri
⁵ Laboratory of Physiological Hygiene and Exercise Science, School of Kinesiology, University of Minnesota, Minneapolis, Minnesota
⁶ Departments of Genetics and Psychiatry, Washington University School of Medicine, St. Louis, Missouri
⁷ Department of Kinesiology, Indiana University, Bloomington, Indiana
⁸ Keck School of Medicine, University of Southern California, Los Angeles, California
⁹ Quebec Heart Institute, Laval Hospital Research Center, Sainte-Foy, Québec, Canada

We investigated the associations between the hepatic lipase gene (LIPC) –514C>T polymorphism and lipases, lipoproteins, and insulin sensitivity (S_i) responses to exercise training. Hepatic lipase and lipoprotein lipase activities, plasma lipoprotein levels, and S_i were measured in the sedentary state and post–exercise training in the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study (n = 662). The LIPC –514C allele frequency was 0.516 (blacks) and 0.796 (whites). Baseline and post–exercise training hepatic lipase activities were 40% higher in CC homozygotes (P < 0.0001) in both races. Black CC homozygotes had lower baseline lipoprotein lipase activity, HDL cholesterol, HDL₃, and apolipoprotein (apo)A-1 concentrations. White CC homozygotes had lower baseline HDL cholesterol, apoA-1, LDL cholesterol, and apoB levels that remained low post–exercise training. Baseline S_i was not associated with the LIPC genotypes. However, training-induced improvements in S_i both in blacks and whites were greater in CC homozygotes (+1.25 ± 0.2 and +0.22 ± 0.2 µU · min^–1 · ml^–1) than in the TT genotype (+0.27 ± 0.3 and –0.97 ± 0.3 µU · min^–1 · ml^–1) (P = 0.008 and P = 0.002, respectively). The LIPC –514C allele was associated with higher hepatic lipase activity in sedentary and physically active states and better S_i responses to regular exercise both in black and white individuals. The benefits from an exercise program on S_i are likely to be substantial in the general population given the high frequency of the LIPC –514C allele, particularly in whites.

Abbreviations: apo, apolipoprotein; CHD, coronary heart disease; HERITAGE, Health, Risk Factors, Exercise Training, and Genetics; LPL, lipoprotein lipase

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