Published online before print January 31, 2002, doi: 10.1161/01.ATV.0000012302.11991.42
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© 2002 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Association Between the PPARA L162V Polymorphism and Plasma Lipid Levels
The Framingham Offspring Study
From the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University (E.S.T., E.J.S., J.M.O), Boston, Mass; Boston University School of Public Health (S.D., L.A.C.) and School of Medicine (P.W.W.), Boston, Mass; Genetic and Molecular Epidemiology Unit (D.C.), Public Health Department, School of Medicine, Universitat de Valencia, Valencia, Spain; The Framingham Heart Study (P.W.W.), Framingham, Mass.
Address correspondence to Prof J.M. Ordovas, Nutrition and Genomics Laboratory, Jean-Mayer USDA Human Nutrition Research Center on Ageing at Tufts University, 711 Washington St, Boston, MA 02111. E-mail ordovas@ hnrc.tufts.edu
Peroxisome proliferator activated receptor (PPAR) alpha is a member of the nuclear receptor superfamily that regulates key proteins involved in fatty acid oxidation, extracellular lipid metabolism, hemostasis, and inflammation. A L162V polymorphism at the PPARA locus has been associated with alterations in lipid and apolipoprotein concentrations. We studied the association among lipids, lipoproteins, and apolipoproteins and the presence of the L162V polymorphism in 2373 participants (1128 men and 1244 women) in the Framingham Offspring Study. The frequency of the less common allele (V162) was 0.069. The V162 allele was associated with increased serum concentrations of total and LDL cholesterol in men (P=0.0012 and P=0.0004, respectively) and apolipoprotein B in men (P=0.009) and women (P=0.03 after adjustment for age, body mass index, smoking, and use of ß-blockers, diuretics or estrogens). Apolipoprotein (apo) C-III concentrations were higher in carriers of the V162 allele. The association of the L162V polymorphism on LDL cholesterol concentration was greatest in those who also carried the E2 allele at the APOE locus and the G allele at the APOC3 3238C>G polymorphism. This suggests that alterations in triglyceride-rich lipoprotein metabolism may be involved in the generation of the increase LDL cholesterol observed with the L162V PPARA polymorphism.
Key Words: PPAR&agr • polymorphism • LDL • apolipoprotein C-III • triglyceride-rich lipoprotein
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