PPARalpha gene variants influenced coronary atherosclerosis progression and ischemic heart disease risk, with V162 allele carriers showing less progression and intron 7 C carriers showing greater risk.
Observational
Yes
Do PPARalpha gene variants influence the progression of coronary atherosclerosis and the risk of ischemic heart disease?
PPARalpha gene variants significantly influence the progression of coronary atherosclerosis and the risk of ischemic heart disease, likely through direct effects on the vessel wall rather than via systemic plasma lipid concentrations.
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 IHD, an effect modulated by the L162V polymorphism CONCLUSIONS: 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.
Flavell et al. (Tue,) conducted a observational in Coronary atherosclerosis and ischemic heart disease. PPARalpha gene variants (L162V and intron 7 G/C) vs. L162 allele homozygotes and intron 7 G allele homozygotes was evaluated on Progression of atherosclerosis and risk of IHD. PPARalpha gene variants influenced coronary atherosclerosis progression and ischemic heart disease risk, with V162 allele carriers showing less progression and intron 7 C carriers showing greater risk.