Cholesterol Esther Transfer Protein
Gene & SNP Summary
Cholesteryl ester transfer protein, encoded by CETP, plays a key role in the metabolism of high-density lipoproteins (HDL). It mediates the exchange of lipids between lipoproteins, resulting in the eventual uptake of cholesterol by hepatocytes (reverse cholesterol transport). High plasma CETP concentration is associated with reduced HDL concentrations and is a strong and independent risk factor for CAD. The 279A allele is associated with reduced plasma CETP levels, increased HDL levels and reduced risk of cardiovascular disease. Conversely, the G allele is associated with increased plasma CETP levels, reduced HDL-C levels and increased cardiovascular disease risk. Individuals with the GG genotype, who have been linked with the least favourable lipid profile, respond particularly well to statin therapy, effectively abolishing the increased risk posed by the genotype. Interestingly AA genotype individuals may not respond as well to respond statin therapy. Additionally, a linoleic acid-enriched, low cholesterol diet is effective in decreasing VLDL-C and LDL-C levels in GA individuals.
CETP, a gene found on the long arm of chromosome 16, encodes cholesteryl ester transfer protein. It is involved in the transfer of lipids such as cholesteryl esters from HDL to apolipoprotein B–containing particles in exchange for triglyceride, and the equimolar transport of triglyceride from VLDL to HDL.
CETP is important in regulating the reverse cholesterol transport, by which excess cholesterol is removed from peripheral tissues and returned to the liver for elimination. Lower levels of CETP are associated with higher HDL cholesterol levels and improved cardiovascular parameters. It is important to note that elaidic acid, which is a major component of trans fat, increases CETP activity.
LoThe G279A SNP has been reported in many gene-environment interaction studies. The CETP 279A allele leads to decreased levels of circulating CETP and has been associated with raised HDL and protection against CVD.
With regards to diet-gene interactions, a majority of the studies focus on examining the effects of dietary fatty acids on the relation of CETP G279A polymorphism and metabolic traits. Other studies considered the SNP in relation to the Mediterranean diet, alcohol intake and plant sterols on lipid profiles and CVD outcomes.
Although the CETP 279 GG genotype carriers exhibited lower HDL-C concentrations compared to A allele carriers, they also showed a better response to dietary interventions than those with the A allele.
Individuals who carry the CETP 279 GG genotype should ensure adherence to the Mediterranean style diet. There appears to be better improvements with regards to HDL-C levels and CVD outcomes when saturated fat is replaced with monounsaturated and polyunsaturated fatty acids (FA), with a focus on omega 3 FA. It is also important for GG genotype individuals to moderate total alcohol intake.
Genetic variations of cholesteryl ester transfer protein and diet interactions in relation to lipid profiles and coronary heartdisease: a systematic review
Mirmiran et al, 2017.