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.
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.


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 > or =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.
Ordovas
Jose M
JM
Nutrition and Genomics Laboratory, Jean Mayer-US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Mass 02111, USA. ordovas@hnrc.tufts.edu
Corella
Dolores
D
Demissie
Serkalem
S
Cupples
L Adrienne
LA
Couture
Patrick
P
Coltell
Oscar
O
Wilson
Peter W F
PW
Schaefer
Ernst J
EJ
Tucker
Katherine L
KL
D000328:Adult; D000368:Aged; D000483:Alleles; D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood / Q000378:metabolism*; D015331:Cohort Studies; D003710:Demography; D004041:Dietary Fats / Q000378:metabolism*; D004734:Energy Metabolism / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008099:Liver / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012044:Regression Analysis; D012306:Risk
D008076:Cholesterol, HDL; D004041:Dietary Fats; D008049:Lipase