APOA5 gene variants, lipoprotein particle distribution, and progression of coronary heart disease: results from the LOCAT study.
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.
Talmud
Philippa J
PJ
Centre for Cardiovascular Genetics, Department of Medicine, British Heart Foundation Laboratories, Royal Free and University College Medical School, London, UK. p.talmud@ucl.ac.uk
Martin
Steve
S
Taskinen
Marja-Riitta
MR
Frick
M Heikki
MH
Nieminen
Markku S
MS
Kesäniemi
Y Antero
YA
Pasternack
Amos
A
Humphries
Steve E
SE
Syvänne
Mikko
M
D000368:Aged; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins / Q000235:genetics*; D001054:Apolipoproteins A; D001161:Arteriosclerosis / Q000097:blood / Q000235:genetics / Q000473:pathology; D003327:Coronary Disease / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D015248:Gemfibrozil / Q000008:administration & dosage / Q000494:pharmacology; D005838:Genotype; D006801:Humans; D008074:Lipoproteins / Q000097:blood* / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D010316:Particle Size; D020641:Polymorphism, Single Nucleotide; D014280:Triglycerides / Q000097:blood
C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins; D001054:Apolipoproteins A; D008074:Lipoproteins; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D015248:Gemfibrozil