CETP, LIPC gene polymorphisms affect atherosclerotic risk
MedWire News: Imbalances between cholesteryl ester transfer protein (CETP) and hepatic lipase (LIPC) activities may modulate the risk for carotid atherosclerosis, research suggests.
The findings show that CETP and LIPC polymorphisms influence the respective hepatic transcript levels and may interact with high-density lipoprotein (HDL) cholesterol levels.
Furthermore, compared with individuals carrying wild-type alleles at both loci, those homozygous for the CETP wild-type allele and heterozygous for the LIPC polymorphism, or homozygous for the LIPC wild-type allele and heterozygous for the CETP polymorphism may be at increased risk for carotid atherosclerosis.
"These findings may be relevant for therapeutic strategies aiming to increase HDL cholesterol by altering the activities of [these] HDL modifying proteins," say Wolfgang Patsch (Paracelsus Medical University, Salzburg, Austria) and colleagues.
The researchers genotyped the -514C>T-LIPC and the CETP-Taq1B polymorphisms in a group of 67 obese women, and in another group consisting of 1549 participants of the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR).
Patsch and team then examined the effects of these polymorphisms on hepatic mRNA expression, plasma lipids and lipoproteins, and carotid atherosclerosis - assessed by intima-media thickness (IMT) and extent of carotid artery plaques.
Overall, the minor alleles of the -514C>T-LIPC and the CETP-Taq1B polymorphisms were present in a respective 23% and 41% of the obese women, and 21% and 41% of the SAPHIR population.
The researchers found that the variant alleles were significantly associated with reduced hepatic levels of LIPC and CETP mRNA in the obese population, accounting for 14.4% and 12.9% of the variability in the respective transcripts.
Reporting in the journal Atherosclerosis, the authors say that the minor allele of both polymorphisms was independently and significantly associated with increased HDL cholesterol and apolipoprotein (apo)A-I levels, while the minor CETP allele was also associated with increased low-density lipoprotein (LDL) cholesterol size and ratio of total/HDL cholesterol.
Of note, Patsch et al found that neither the -514C>T-LIPC nor the CETP-Taq1B polymorphism showed significant independent associations with carotid IMT or lesion size or number.
However, compared with patients carrying wild-type alleles at both loci, those homozygous for the CETP wild-type allele but heterozygous for the LIPC polymorphism were at a 55% increased risk for carotid atherosclerosis, and those heterozygous for the CETP polymorphism but homozygous for the LIPCLIPC wild-type allele were at a 39% increased risk.
The team concludes: "Our data suggest that the combined effects of these genotypes modulate the risk for carotid atherosclerosis."
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By Nikki Withers