Abstract:
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 > 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.
journal_name
Circulationjournal_title
Circulationauthors
Ordovas JM,Corella D,Demissie S,Cupples LA,Couture P,Coltell O,Wilson PW,Schaefer EJ,Tucker KLdoi
10.1161/01.cir.0000036597.52291.c9subject
Has Abstractpub_date
2002-10-29 00:00:00pages
2315-21issue
18eissn
0009-7322issn
1524-4539journal_volume
106pub_type
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