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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #176039
Title: POLYUNSATURATED FATTY ACIDS INTERACT WITH THE PPARA-L162V POLYMORPHISM TO AFFECT PLASMA TRIGLYCERIDE AND APOLIPOPROTEIN C-III CONCENTRATIONS IN THE FRAMINGHAM HEART STUDY

Author
item TAI, E - TUFTS/HNRCA
item CORELLA, DOLORES - TUFTS/HNRCA
item DEMISSIE, SERKALEM - BOSTON UNIVERSITY
item CUPPLES, L - BOSTON UNIVERSITY
item COLTELL, OSCAR - TUFTS/HNRCA
item Schaefer, Ernst
item Tucker, Katherine
item Ordovas, Jose

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/6/2004
Publication Date: 3/1/2005
Citation: Tai, E.S., Corella, D., Demissie, S., Cupples, L.A., Coltell, O., Schaefer, E., Tucker, K., Ordovas, J.M. 2005. Polyunsaturated fatty acids interact with the PPARA-L162V polymorphism to affect plasma triglyceride and apolipoprotein C-III concentrations in the Framingham Heart Study. Journal of Nutrition. 135:397-403.

Interpretive Summary: There is an increased interest to understand the factors that regulate the expression of our genes. Some of them are known nuclear transcription factors and are involved in the expression of genes following their activation by external factors such as nutrients. One of them is known as peroxisome proliferator-activated receptor alpha (PPARA). The gene coding for this transcription factor contains several mutations that have been associated with different cardiovascular risk factors including plasma lipids, obesity and diabetes status. We investigated one of these mutations to ascertain the potential interaction between this gene, plasma lipids and dietary factors in the population enrolled in the Framingham study (1003 men and 1103 women). Our data clearly demonstrate that the effect of a common variant at the PPARA gene known as the L162V polymorphism is associated with plasma triglyceride concentrations in a manner that is modulated but the intake of polyunsaturated fatty acids, with high intake of these fatty acids triggering lower triglycerides only in carriers of the 162V form of this gene. Our results support the relevance of knowing the genetic make up in order to provide more precise and successful dietary recommendations for disease prevention.

Technical Abstract: Peroxisome proliferator-activated receptor alpha (PPARA) is a nuclear transcription factor regulating multiple genes involved in lipid metabolism. It has been shown that a common leucine to valine (L162V) substitution at the PPARA alpha gene (PPARA) is functional and affects transactivation activity of PPARA ligands, such as polyunsaturated fatty acids (PUFA), on a concentration-dependent basis. Therefore, our aim was to examine this gene-nutrient interaction on plasma lipid-related variables in a population-based study consisting of 1003 men and 1103 women participating in the Framingham cohort and consuming their habitual diets. We found statistically significant gene-nutrient interactions between the L162V polymorphism and total PUFA intake modulating plasma triglycerides (TG; P<0.05) and apolipoprotein C-III (apoC-III; P<0.05) concentrations. The 162V allele being associated with greater TG and apoC-III concentrations only in subjects consuming a low PUFA diet (below the population mean, 6% of energy). However, when PUFA intake was high, carriers of the 162V allele had lower concentrations. This interaction showed a strong dose-response effect being statistically significant even when PUFA intake was considered as continuous (P=0.031 for TG and P<0.001 for apoC-III). Thus, when PUFA intake was <4%, 162V allele carriers had ' 28% higher TG than did 162L homozygotes (P<0.01). Conversely, when PUFA intake was >8%, TG in 162V allele carriers were 4% lower than those of 162L homozygotes. Similar results were obtained for n-6 and n-3 fatty acids. Our data show that the effect of the L162V polymorphism on plasma TG and apoC-III concentrations depends on the dietary PUFA, with high intake triggering lower TG in carriers of the 162V allele.