Skip to main content
ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #145166
Title: DIETARY FAT INTAKE DETERMINES THE EFFECT OF A COMMON POLYMORPHISM IN THE HEPATIC LIPASE GENE PROMOTER ON HIGH-DENSITY...METABOLISM: EVIDENCE OF A STRONG DOSE EFFECT IN THIS GENE-NUTRIENT INTERACTION IN THE FRAMINGHAM STUDY

Author
item ORDOVAS, JOSE - HNRCA
item CORELLA, DOLORES - HNRCA
item DEMISSIE, SERKALEM - BOSTON U
item CUPPLES, ADRIENNE - BOSTON U
item COUTURE, PATRICK - HNRCA
item COLTELL, OSCAR - HNRCA
item WILSON, PETER - BOSTON U
item SCHAEFER, ERNST - HNRCA
item TUCKER, KATHERINE - HNRCA

Submitted to: Circulation
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/21/2002
Publication Date: 10/1/2002
Citation: ORDOVAS, J.M., CORELLA, D., DEMISSIE, S., CUPPLES, A.L., COUTURE, P., COLTELL, O., WILSON, P.W., SCHAEFER, E.J., TUCKER, K.L. DIETARY FAT INTAKE DETERMINES THE EFFECT OF A COMMON POLYMORPHISM IN THE HEPATIC LIPASE GENE PROMOTER ON HIGH-DENSITY...METABOLISM: EVIDENCE OF A STRONG DOSE EFFECT IN THIS GENE-NUTRIENT INTERACTION IN THE FRAMINGHAM STUDY. CIRCULATION. 106(18):23-5,2002.

Interpretive Summary: Diet is the cornerstone for prevention of cardiovascular disease. General recommendations are given to the general public in terms of which diet should be used to lower the risk of heart disease. However, it is not know how many people benefit from those global recommendations and it has even suggested that they could be harmful to some. For this reason scientists are actively looking for ways to be able to give more individualized as successful recommendations. It is known that people do not respond to diet in the same manner and that genetics play a role in these individual differences. Hepatic Lipase (HL) is a key player in the metabolism of plasma high-density lipoproteins (HDL), known also as ¿good¿ cholesterol. We have studied a common gene mutation in the HL gene to learn whether this mutation determines how the levels of the good cholesterol are modified by dietary fat. For this purpose, we examined this topic in subjects from the well-known Framingham Heart Study. We found that in people who have the allele called T an increased intake of fat, specifically saturated fat, results in lower levels of the good HDL-C, whereas the opposite effect is observed in subjects who have the C allele. Therefore, T subjects are at much higher risk of heart disease when they consume the current diets in the US. Our data is an important step towards the understanding of dietary response and our ability to provide more successful dietary advice.

Technical Abstract: 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. The T allele at a ¿514C/T polymorphism at this gene has been associated with decreased HL activity and increased HDL-C. However, the effect is variable among populations. 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 levels only in subjects consuming <30% of energy from fat (P<0.001). When total fat intake was > or =30% of energy, mean HDL-C levels 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, but not for polyunsaturated fat. In conclusion, 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.