Genetics
CETP variant R451Q lowers carotid artery thickness in men, while I405V harms only heavy drinkers (Eur J Clin Invest 2000)
Original title: Cholesteryl ester transfer protein gene polymorphisms are associated with carotid atherosclerosis in men
This study examined the prevalence of CETP I405V and R451Q polymorphisms and their association with carotid atherosclerosis, measured by intima-media thickness (IMT) via ultrasonography, in a population sample of 515 men and women, with genotyping by PCR. The Q451 allele, previously linked to high plasma CETP activity in men, was associated with significantly lower IMT in men (P=0.001). The VV405 genotype was associated with lower plasma CETP activity than the II405 genotype (P less than 0.01). A significant interaction was found between alcohol consumption and I405V genotype on IMT in men (P=0.013); once this interaction term was included, the I405V genotype itself also significantly affected IMT (P=0.008), with the VV405 genotype appearing most harmful in men with the highest alcohol consumption.
Original abstract
Background: The cholesteryl ester transfer protein (CETP) is involved in the reverse cholesterol transport and is therefore a candidate gene for atherosclerosis.
Design: The prevalences of the I405V and the R451Q polymorphisms were studied in a population sample of 515 men and women. Genotypes were determined by PCR and carotid atherosclerosis by ultrasonography as the mean intima-media thickness (IMT) of the carotid arteries.
Results: The Q451 allele was associated with significantly lower intima media thickness in men (P = 0.001). The Q451 allele was, in our earlier study, associated with high plasma CETP activity in men. The VV405 genotype was associated with lower plasma CETP activity compared with the II405 genotype (P < 0.01 for the difference). In the general linear model general factorial procedure the interaction between alcohol consumption and the I405V genotype on IMT was significant (P = 0.013) in men, and when the interaction term was taken into the model the I405V genotype also significantly affected IMT (P = 0.008). The VV405 genotype seems to be most harmful for men with the highest alcohol consumption.
Conclusions: We describe two polymorphisms of the CETP gene associated with intima media thickness in men. A significant interaction was found between alcohol consumption and the I405V genotype on IMT.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.