Genetics
CETP and hepatic lipase gene variants interact to raise carotid atherosclerosis risk in 1,549-person SAPHIR cohort (Atherosclerosis 2011)
Original title: Cholesteryl ester transfer protein and hepatic lipase gene polymorphisms: effects on hepatic mRNA levels, plasma lipids and carotid atherosclerosis
Researchers studied the CETP-Taq1B and hepatic lipase (LIPC) -514C>T polymorphisms in 67 obese women, measuring hepatic CETP and LIPC transcript levels, and in 1549 participants of the SAPHIR population study, assessing carotid intima-media thickness and plaque extent. In the obese women, the CETP-Taq1B and LIPC-514C>T variant alleles were associated with reduced hepatic CETP and LIPC mRNA, respectively, together explaining 12.9% and 14.4% of transcript variability. In SAPHIR, CETP-Taq1B independently affected LDL particle diameter, HDL and LDL cholesterol, apolipoproteins AI and B, and the cholesterol/HDL-C ratio, and the two polymorphisms interacted at the level of HDL cholesterol; subjects with a discordant genotype combination (heterozygous at one locus, wild-type homozygous at the other) had increased carotid atherosclerosis risk (both P<0.05) compared with subjects homozygous wild-type at both. The authors conclude imbalances between CETP and LIPC activity may modulate carotid atherosclerosis risk.
Original abstract
Objective: HDL modifying effects of cholesteryl ester transfer protein (CETP) and hepatic lipase (LIPC) depend in part on each other. We studied associations of CETP-Taq1B and -514C>T-LIPC polymorphisms with hepatic mRNA levels, and their combined effects on plasma lipids and carotid atherosclerosis.
Methods: We genotyped the CETP-Taq1B and the -514C>T-LIPC polymorphisms in 67 obese women in whom hepatic CETP and LIPC transcript levels were determined as well as in 1549 participants of the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR). Carotid atherosclerosis was assessed by intima-media thickness and extent of plaques (B-score) of the carotid arteries.
Results: In obese women, CETP-Taq1B and -514C>T-LIPC variant alleles were associated with reduced hepatic levels of CETP and LIPC mRNA, respectively. The CETP and LIPC polymorphisms accounted for 12.9 and 14.4% of the variability in respective transcripts. In the SAPHIR population, CETP-Taq1B showed independent effects on LDL diameter, HDL and LDL cholesterol, apolipoproteins AI and B and cholesterol/HDL cholesterol, while -514C>T-LIPC revealed independent effects on HDL cholesterol and apolipoprotein AI. The two polymorphisms displayed interactions at the level of HDL cholesterol. Compared to subjects carrying wild-type alleles at both loci, subjects homozygous for the CETP wild-type allele, but heterozygous for the LIPC polymorphism and subjects heterozygous for the CETP polymorphism, but homozygous for the LIPC wild-type allele showed an increased risk of carotid atherosclerosis (both P<0.05).
Conclusions: CETP and LIPC polymorphisms influence the respective hepatic transcript levels, demonstrate interactions on HDL cholesterol and suggest that imbalances between CETP and LIPC activities may modulate the risk of carotid atherosclerosis.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.