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. METHODS AND 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.