Abstract
Animal and human studies support a role for apolipoprotein A-V (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 -1131C 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, IDL-cholesterol (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.
Highlights
Animal and human studies support a role for apolipoprotein A-V in triglyceride (TG) metabolism
The lipid compositional data suggest that this reflects an increase in VLDL-TG, and the higher levels of VLDL components, with the exception of phospholipids and apoB, are corroborated by the significant increase in total VLDL mass
The protein content of VLDL was associated with genotype, the levels of apoB did not differ among genotypes, which might reflect a change in apoE and/or apoC-III content
Summary
Animal and human studies support a role for apolipoprotein A-V (apoA-V) in triglyceride (TG) metabolism. Compared with ؊1131TT men (n ؍242), carriers of the ؊1131C 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 Ͻ 0.05)]. Compared with 19SS men (n ؍268), 19W carriers (n ؍44) had higher intermediate density lipoprotein (IDL)TG, IDL-cholesterol (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. 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.—Talmud, P.
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