Apolipoprotein B gene polymorphisms, lipoproteins and coronary atherosclerosis: a study of young myocardial infarction survivors and healthy population-based individuals.
Association studies were carried out in a sample of 87 patients from Sweden who had survived a myocardial infarction (MI) before the age of 45, and 91 age-matched healthy individuals, to compare the impact of polymorphisms at the apolipoprotein (apo) E and B gene loci on among-individual differences in plasma lipid traits and progression of atherosclerosis. In the group of healthy individuals, polymorphisms creating the common apo E isoforms were, as expected, associated with significant differences in total and low density lipoprotein (LDL) cholesterol (11.7% and 11.6% of sample variance). For apo B, the polymorphism with the largest effect on apo B levels (16% of sample variance) was the C to T transition 265 bp 5' of the cap site, in the promoter (detectable by MspI). Both this polymorphism and the threonine2488 neutral substitution (detectable by XbaI) were associated with significant effects on LDL-cholesterol (8.3% and 9.3% of sample variance, respectively). The asparagine/serine4311 polymorphism was associated with a significant effect on high density lipoprotein (HDL) cholesterol alone, and there was no significant association with the glutamate/lysine4154 polymorphism (detectable by EcoRI) or the leucine-alanine-leucine (LAL) insertion/deletion polymorphism in the signal peptide. In the patients, polymorphisms creating the three common apo E isoforms were associated with large effects on cholesterol, apo B and triglyceride levels (19.9%, 20.3% and 23.9% of sample variance) of similar magnitude as in the healthy individuals. Apo B polymorphisms were found to be associated with much smaller effects on lipid traits than in the healthy individuals. The only significant association was between the asparagine/serine4311 polymorphism and HDL-triglyceride levels. However, global severity of coronary atherosclerosis at the first angiography was found to be significantly associated with the LAL insertion/deletion polymorphism (P = 0.008). Thus variation at the apo B gene locus is associated with the development of atherosclerosis, but the data suggests that this may act through mechanisms not directly related to effects on measured lipid traits.
Charing Cross Sunley Research Centre, Hammersmith, London, U.K.
R
R
Peacock
A
A
Dunning
A
A
Hamsten
P
P
Tornvall
S
S
Humphries
P
P
Talmud
D000328:Adult; D000595:Amino Acid Sequence; D001055:Apolipoproteins B / Q000235:genetics*; D001483:Base Sequence; D003324:Coronary Artery Disease / Q000097:blood / Q000150:complications / Q000235:genetics*; D004247:DNA / Q000235:genetics; D006801:Humans; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008969:Molecular Sequence Data; D009203:Myocardial Infarction / Q000097:blood / Q000150:complications / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length
D001055:Apolipoproteins B; D008055:Lipids; D008074:Lipoproteins; D004247:DNA