|Lai, Chao Qiang|
Submitted to: Atherosclerosis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/10/2009
Publication Date: 3/25/2009
Citation: Smith, C.E., Arnett, D.K., Tsai, M.Y., Lai, C., Parnell, L.D., Shen, J., Laclaustra, M., Junyent, M., Ordovas, J.M. 2009. Physical inactivity interacts with an endothelial lipase polymorphism to modulate high density lipoprotein cholesterol in the GOLDN study. Atherosclerosis.206:500-504. Interpretive Summary: Levels of high density lipoprotein (HDL) cholesterol (HDL-C, the "good" cholesterol) in blood is highly dependent on genetics but is also influenced by environmental factors such as physical activity, diet and tobacco use. The response of HDL-C to exercise varies among individuals and this variability may arise from certain genetic variants in key regulators of HDL biochemistry. One such regulator is LIPG, endothelial lipase, which catalyzes the breakdown of triacylglycerol. We examined associations between genetic variants of the LIPG gene, HDL levels and television viewing/computer use ("screen time") as a marker for physical inactivity in a population. Subjects consisted of 539 White men and 584 women (mean+/-SD,49+/-16 y) participating in the GOLDN study. No association was observed between the LIPG variants and HDL levels independent of screen time. Using a sophisticated statistical model indicated that the amount of screen time shows a relationship to HDL, but only in women. Specifically, when screen time was >/=2.6 hours/day, concentrations of total HDL-C were lower (less healthy) while levels of small LDL were higher (also less healthy) only in subjects with a particular version of the LIPG gene (TT at variant LIPG i24582). In summary, an interaction between physical activity and a gene variant of LIPG exerts influence on HDL and some LDL measures. Therefore, increasing physical activity may protect those women whose LIPG genotype is TT at variant i24582 from cardiovascular risk by increasing HDL levels.
Technical Abstract: BACKGROUND: Plasma high density lipoprotein (HDL) cholesterol (HDL-C) concentration is highly heritable but is also modifiable by environmental factors including physical activity. HDL-C response to exercise varies among individuals, and this variability may be associated with genetic polymorphisms in key regulators of HDL metabolism including endothelial lipase (LIPG). METHODS: We examined associations between variants LIPG T111I(rs2000813) and LIPG i24582(rs6507931), HDL and television viewing/computer use ("screen time") as a marker for physical inactivity in a population with high prevalence of metabolic syndrome. Subjects consisted of 539 White men and 584 women (mean+/-SD,49+/-16 y) participating in the GOLDN study. RESULTS: We did not observe an association with either LIPG SNP and HDL independently of screen time. In multi-adjusted linear regression models, HDL interacted significantly with screen time as a continuous variable in LIPG i24582 subjects with TT genotype (p<0.05). By dichotomizing screen time into high and low levels, we found significant genotype-associated differences in HDL in women but not men. When screen time was >/=2.6 hours/day, concentrations of total HDL-C, large HDL, large low density lipoprotein (LDL) were lower, concentration of small LDL was higher and HDL and LDL particle sizes were smaller in subjects with LIPG i24582 TT compared to CT and CC subjects (P<0.05). CONCLUSIONS: We found a significant gene-physical inactivity interaction for HDL and some LDL measures for the LIPG i24582 polymorphism. Higher levels of physical activity may be protective for HDL-C concentrations and low activity detrimental in LIPG i24582 TT individuals, especially in women.