Common promoter C516T polymorphism in the ApoB gene is an independent predictor of carotid atherosclerotic disease in subjects presenting a broad range of plasma cholesterol levels.
OBJECTIVE
A common polymorphism in the promoter of the apolipoprotein B (apoB) gene, a C to T change at position -516, increases the transcription rate of apoB, resulting in elevated circulating levels of low-density lipoprotein (LDL) cholesterol.


RESULTS
We tested the hypothesis that carriers of the -516T allele, who may display consistent elevation in plasma cholesterol over their lifetime, may present more extensive atherosclerotic disease than noncarriers. Genotyping of the apoB 516 C/T promoter polymorphism was performed in 326 subjects at low cardiovascular risk. Homozygotes for allele T displayed higher plasma levels of apoB and LDL than did heterozygotes. Furthermore, both homozygotes and heterozygotes for allele T exhibited higher plasma levels of apoB and LDL than did homozygotes for allele C (P<0.0001). In addition, homozygotes for allele T displayed higher carotid intima-media thickness (IMT) than subjects who were heterozygous. Moreover, both groups had higher carotid IMT than subjects of genotype -516C/C (P<0.001). Only age, high-density lipoprotein, and the presence of allele T were identified as independent predictors of the presence of carotid plaque. No association existed between the polymorphism and plasma concentrations of triglycerides, high-density lipoprotein, or apoAI.


CONCLUSIONS
Our data indicate that a C to T change at position -516 of the apoB gene is independently associated with the presence of carotid atherosclerotic disease. Identification of the -516C/T polymorphism may therefore contribute to the estimation of overall cardiovascular risk.
Sposito
Andrei C
AC
Dyslipoproteinemia and Atherosclerosis Research Unit, National Institute for Health and Medical Research (INSERM), Paris, France. sposito@zerbini.org.br
Gonbert
Sophie
S
Turpin
Gerard
G
Chapman
M John
MJ
Thillet
Joëlle
J
D001053:Apolipoproteins / Q000097:blood; D001055:Apolipoproteins B / Q000235:genetics*; D002340:Carotid Artery Diseases / Q000097:blood* / Q000235:genetics*; D002784:Cholesterol / Q000097:blood*; D003596:Cytosine / Q000378:metabolism*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011237:Predictive Value of Tests; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013941:Thymine / Q000378:metabolism*; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology
D001053:Apolipoproteins; D001055:Apolipoproteins B; D008055:Lipids; D003596:Cytosine; D002784:Cholesterol; D013941:Thymine