Published online before print October 21, 2002, doi: 10.1161/01.CIR.0000036597.52291.C9
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(Circulation. 2002;106:2315.)
© 2002 American Heart Association, Inc.
Clinical Investigation and Reports |
Dietary Fat Intake Determines the Effect of a Common Polymorphism in the Hepatic Lipase Gene Promoter on High-Density Lipoprotein Metabolism
Evidence of a Strong Dose Effect in This Gene-Nutrient Interaction in the Framingham Study
From the Nutrition and Genomics Laboratory (J.M.O., D.C., O.C.), Lipid Metabolism Laboratory (E.J.S., P.C.) and the Epidemiology Program (K.L.C.), Jean Mayer-US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Mass; the Boston University School of Public Health (S.D., L.A.C.) and School of Medicine, Boston, Mass; and the Framingham Heart Study, Framingham, Mass (P.W.F.W.).
Correspondence to J.M. Ordovas, Nutrition and Genomics Laboratory, JM-USDA-HNRCA, Tufts University, 711 Washington St, Boston, MA 02111. E-mail ordovas{at}hnrc.tufts.edu
Background— Gene-nutrient interactions affecting high-density lipoprotein cholesterol (HDL-C) concentrations may contribute to the interindividual variability of the cardiovascular disease risk associated with dietary fat intake. Hepatic lipase (HL) is a key determinant of HDL metabolism. Four polymorphisms in linkage disequilibrium have been identified in the HL gene (LIPC), defining what is known as the -514T allele. This allele has been associated with decreased HL activity and increased HDL-C concentrations. However, the effect is variable among populations.
Methods and Results— We have examined interaction effects between the -514(C/T) LIPC polymorphism, dietary fat, and HDL-related measures in 1020 men and 1110 women participating in the Framingham Study. We found a consistent and highly significant gene-nutrient interaction showing a strong dose-response effect. Thus, the T allele was associated with significantly greater HDL-C concentrations only in subjects consuming <30% of energy from fat (P<0.001). When total fat intake was 
30% of energy, mean HDL-C concentrations were lowest among those with the TT genotype, and no differences were observed between CC and CT individuals. We found similar gene-nutrient interactions when the outcome variables were HDL2-C (P<0.001), large HDL subfraction (P<0.001), or HDL size (P=0.001). These interactions were seen for saturated and monounsaturated fat intakes (highly correlated with animal fat in this population), but not for polyunsaturated fat.
Conclusions— Dietary fat intake modifies the effect of the -514(C/T) polymorphism on HDL-C concentrations and subclasses. Specifically, in the Framingham Study, TT subjects may have an impaired adaptation to higher animal fat diets that could result in higher cardiovascular risk.
Key Words: lipids • lipoproteins • diet • fatty acids • genetics
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