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Journal of Lipid Research, Vol. 45, 750-756, April 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology
* Centre for Cardiovascular Genetics, Department of Medicine, British Heart Foundation Laboratories, Royal Free and University College Medical School, London, UK
Division of Cardiology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
Department of Medicine and Biocenter Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
** Department of Medicine, Tampere University Hospital, Tampere, Finland
1 To whom correspondence should be addressed. e-mail: p.talmud{at}ucl.ac.uk
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.
Supplementary key words apolipoprotein A-V • lipid subfractions • very low density lipoprotein • intermediate density lipoprotein • progression of atherogenesis • Lopid Coronary Angiography Trial • gemfibrozil • pharmacogenetics
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