Flavell, DM and Jamshidi, Y and Hawe, E and Torra, LP and Taskinen, MR and Frick, MH and Nieminen, MS and Kesaniemi, YA and Pasternack, A and Staels, B and Miller, G and Humphries, SE and Talmud, PJ and Syvanne, M (2002) Peroxisome proliferator-activated receptor alpha gene variants influence progression of coronary atherosclerosis and risk of coronary artery disease. CIRCULATION , 105 (12) 1440 - 1445. 10.1161/01.CIR.0000012145.80593.25.
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Background-Peroxisome proliferator-activated receptor alpha (PPARalpha) regulates the expression of genes involved in lipid metabolism and inflammation, making it a candidate gene for atherosclerosis and ischemic heart disease (IHD).Methods and Results-We investigated the association between the leucine 162 to valine (L162V) polymorphism and a G to C transversion in intron 7 of the PPARalpha gene and progression of atherosclerosis in the Lopid Coronary Angiography Trial (LOCAT), a trial examining the effect of gemfibrozil treatment on progression of atherosclerosis after bypass surgery and on risk of IHD in the second Northwick Park Heart Study (NPHS2), a prospective study of healthy middle-aged men in the United Kingdom. There was no association with plasma lipid concentrations in either study. Both polymorphisms influenced progression of atherosclerosis and risk of IHD. V162 allele carriers had less progression of diffuse atherosclerosis than did L162 allele homozygotes with a similar trend for focal atherosclerosis. Intron 7 C allele carriers had greater progression of atherosclerosis than did G allele homozygotes. The V162 allele attenuated the proatherosclerotic effect of the intron 7 C allele. Homozygotes for the intron 7 C allele had increased risk of lHD, an effect modulated by the L162V polymorphismConclusions-The PPARalpha gene affects progression of atherosclerosis and risk of IHD. Absence of association with plasma lipid concentrations suggests that PPARalpha affects atherosclerotic progression directly in the vessel wall.
|Title:||Peroxisome proliferator-activated receptor alpha gene variants influence progression of coronary atherosclerosis and risk of coronary artery disease|
|Keywords:||atherosclerosis, genetics, coronary disease, VEIN-GRAFT ATHEROSCLEROSIS, VASCULAR ENDOTHELIAL-CELLS, TISSUE FACTOR EXPRESSION, MONOCYTIC THP-1 CELLS, PPAR-GAMMA ACTIVATORS, FUNCTIONAL-CHARACTERIZATION, INFLAMMATION CONTROL, HDL CHOLESTEROL, BYPASS SURGERY, HEART-DISEASE|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of) > Metabolism and Experimental Therapeutics|
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
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