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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:2192.)
© 2004 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

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

Andrei C. Sposito; Sophie Gonbert; Gerard Turpin; M. John Chapman; Joëlle Thillet

From the Dyslipoproteinemia and Atherosclerosis Research Unit (U.551) (A.C.S., S.G., M.J.C., J.T.), National Institute for Health and Medical Research (INSERM), Paris, and the Department of Endocrinology and Metabolism (S.G., G.T.), APHP Hôpital de La Pitié-Salpetrière, France; and the Heart Institute (InCor) (A.C.S.), Zerbini Foundation, Brasilia, Brazil.

Correspondence to Dr Andrei C. Sposito, Instituto do Coração (InCor)–Fundação Zerbini, Estrada do Contorno do Bosque–Cruzeiro Novo, Brasilia, DF, Brazil, 70685-700. E-mail sposito{at}zerbini.org.br

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.

The common –516C/T polymorphism in the apolipoprotein B (apoB) gene increases the transcription rate of apoB, resulting in elevated circulating levels of low-density lipoprotein. A C to T change at position –516 in the apoB gene is independently associated with the presence of carotid atherosclerotic disease. Identification of this polymorphism may contribute to estimation of global cardiovascular risk.

Key Words: apolipoprotein B • polymorphism • carotid disease • atherosclerosis

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