Talmud, PJ and Martin, S and Taskinen, MR and Frick, MH and Nieminen, MS and Kesaniemi, YA and Pasternack, A and Humphries, SE and Syvanne, M (2004) APOA5 gene variants, lipoprotein particle distribution, and progression of coronary heart disease: results from the LOCAT study. J LIPID RES , 45 (4) 750 - 756. 10.1194/jlr.M300458-JLR200.
Animal and human studies support a role for apolipoprotein AN (apoA-V) in triglyceride (TG) metabolism. We examined the relationship of APOA5 -1131T>C and S19W with lipid subfractions and progression of atherosclerosis in the Lopid Coronary Angiography Trial. Compared with -1131TT men (n = 242), carriers of the -1131 C allele (n = 54) had significantly higher total TG (P = 0.03), reflected in significantly increased VLDL mass [higher VLDL-TG, VLDL-cholesterol, VLDL-protein, and surface lipids (all P < 0.05)]. Because apoB levels were unaffected by genotype, this suggests an increase in VLDL size and not number. Compared with 19SS men (n = 268), 19W carriers (n = 44) had higher intermediate density lipoprotein (IDL)TG, IDIrcholesterol (P = 0.04), and IDL-surface components [free cholesterol (P = 0.005) and phospholipids (P = 0.017)] but not protein content, suggesting an increase in IDL lipid enrichment resulting in an increase in IDL size. 19W carriers also showed a trend toward increased progression of atherogenesis, as measured by change in average diameter of segments (-0.46 +/- 0.011 mm compared with -0.016 +/- 0.006 mm) in 19SS men (P = 0.08). There was no effect of genotype on the response of these parameters to gemfibrozil treatment. These results shed new light on the role of APOA5 variants in TG metabolism and coronary heart disease risk.
|Title:||APOA5 gene variants, lipoprotein particle distribution, and progression of coronary heart disease: results from the LOCAT study|
|Open access status:||An open access publication|
|Keywords:||apolipoprotein A-V, lipid subfractions, very low density lipoprotein, intermediate density lipoprotein, progression of atherogenesis, Lopid Coronary Angiography Trial, gemfibrozil, pharmacogenetics, APOLIPOPROTEIN A-V, VEIN-GRAFT ATHEROSCLEROSIS, PLASMA TRIGLYCERIDE LEVELS, HDL CHOLESTEROL, BYPASS SURGERY, ARTERY-DISEASE, MEN, POLYMORPHISM, GEMFIBROZIL, PROMOTER|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science|
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