CETP

Official Full Name

cholesteryl ester transfer protein

Organism

Homo sapiens

GeneID

1071

Background

The protein encoded by this gene is found in plasma, where it is involved in the transfer of cholesteryl ester from high density lipoprotein (HDL) to other lipoproteins. Defects in this gene are a cause of hyperalphalipoproteinemia 1 (HALP1). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2013]

Synonyms

BPIFF; HDLCQ10;

Bio Chemical Class

Bactericidal permeability increasing protein

Protein Sequence

MLAATVLTLALLGNAHACSKGTSHEAGIVCRITKPALLVLNHETAKVIQTAFQRASYPDITGEKAMMLLGQVKYGLHNIQISHLSIASSQVELVEAKSIDVSIQNVSVVFKGTLKYGYTTAWWLGIDQSIDFEIDSAIDLQINTQLTCDSGRVRTDAPDCYLSFHKLLLHLQGEREPGWIKQLFTNFISFTLKLVLKGQICKEINVISNIMADFVQTRAASILSDGDIGVDISLTGDPVITASYLESHHKGHFIYKNVSEDLPLPTFSPTLLGDSRMLYFWFSERVFHSLAKVAFQDGRLMLSLMGDEFKAVLETWGFNTNQEIFQEVVGGFPSQAQVTVHCLKMPKISCQNKGVVVNSSVMVKFLFPRPDQQHSVAYTFEEDIVTTVQASYSKKKLFLSLLDFQITPKTVSNLTESSSESVQSFLQSMITAVGIPEVMSRLEVVFTALMNSKGVSLFDIINPEIITRDGFLLLQMDFGFPEHLLVDFLQSLS

Open

Disease

Arterial occlusive disease, Cardiovascular disease, Chronic arterial occlusive disease, Dyslipidemia, Hyper-lipoproteinaemia, Inborn lipid metabolism error, Myocardial infarction

Approved Drug

Clinical Trial Drug

8 +

Discontinued Drug

6 +

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Detailed Information

Found on human chromosome 16, the CETP gene codes for a glycoprotein, mostly produced in the liver and released into the circulation. By allowing the two-way interchange of cholesterol esters and triglycerides among many kinds of lipoprotein particles, CETP is fundamental for lipid metabolism. It especially moves triglycerides in the opposite direction, from VLDL to HDL, from high-density lipoproteins (HDL) to low-density lipoproteins (LDL), and very low-density lipoproteins (VLDL). Maintaining lipid balance in the body and restructuring and composition of plasma lipoproteins depend on this mechanism.

HDL levels in the blood directly change with CETP activity. High CETP activity causes cholesterol esters from HDL to LDL and VLDL to migrate, hence lowering HDL levels. Particularly in the treatment of disorders like coronary atherosclerosis, CETP is seen as a possible pharmacological target as this process is strongly connected to the development of cardiovascular illnesses.

Relationship between CETP and Cardiovascular Diseases

Extensive study now revolves mostly around the link between CETP and cardiovascular health. Many studies have shown that the incidence and progression of cardiovascular disorders like atherosclerosis and coronary heart disease are rather strongly correlated with CETP activity. The HDL level decreases with increasing CETP activity, which can raise the atherosclerosis risk.

Scientists have discovered in a series of genome association studies that several variants in the CETP gene correlate with coronary heart disease incidence. For instance, several single nucleotide polymorphisms (SNPs) in the CETP gene have been linked to higher HDL-C levels; these variants could therefore help lower the risk of coronary heart disease. Moreover, the CETP gene is quite tightly linked to other cardiovascular risk factors like diabetes, obesity, and hypertension.

Emerging therapeutic approaches with great interest are CETP inhibitors. HDL-C levels may be raised by lowering CETP activity, therefore hypothetically lowering the atherosclerosis risk. While certain medications, such as obicetrapib, have demonstrated encouraging clinical benefits and are advancing into further clinical trial phases, early studies failed to show significant changes in cardiovascular outcomes with several CETP inhibitors.

Relationship of CETP with Other Diseases

Apart from cardiovascular ailments, CETP function is also tightly correlated with aging-related disorders and neurodegenerative diseases. Research on CETP polymorphism have shown a correlation between it and the onset and evolution of Alzheimer's disease (AD). For instance, resistance to cognitive deterioration is linked in the CETP gene to the I405V (rs5882) polymorphism. In senior populations, those with the V allele specifically show a slower phase of cognitive deterioration.

Figure 1 describes the role of Cholesteryl Ester Transfer Protein (CETP) in modulating lipid levels, its impact on cardiovascular and brain health, and its potential link to Alzheimer disease through changes in LDL, HDL, and cerebrovascular health. Figure 1. Cholesteryl Ester Transfer Protein (CETP) and Alzheimer's Disease. (Poliakova T, et al., 2023)

Furthermore, influencing lipid metabolism in the brain and hence influencing the course of neurodegenerative disorders is CETP activity. Small vascular stroke and leukoaraiosis are two brain disorders linked in certain clinical and genetic investigations to the CETP gene. These results underline even more the possible function of CETP in aging and neurodegenerative disorders.

Polymorphism of the CETP Gene and Individual Differences

Apart from influencing lipid metabolism, CETP gene polymorphism may also be linked to individual variation in the risk of neurological disorders and cardiovascular diseases. For example, the variance at the rs5882 locus is correlated with many health markers including cognitive decline, HDL-C levels, and risk of coronary heart disease. The rs5882T allele may raise men's risk of cardiovascular events; in women, no notable correlation is seen.

Furthermore, various variants of the CETP gene might be linked to varying cardiovascular disease risks across ethnic populations. For European groups, for instance, the rs5882 variant may raise the incidence of Alzheimer's disease; in Asian populations, no clear association has been seen. The variety of the CETP gene and its effects on different illnesses show the possibilities of genomics in individualized medicine, therefore offering a fresh understanding of disease prevention and therapy.

Prospects of CETP as a Therapeutic Target

In pharmaceutical research, CETP inhibitors as a fresh treatment approach have drawn lot of interest. Particularly in terms of raising HDL-C levels and reducing LDL-C levels, several CETP inhibitors have demonstrated excellent results in clinical studies While some novel CETP inhibitors, including obicetrapib, have shown encouraging results, particularly in treating cardiovascular disorders, certain clinical studies of CETP inhibitors have been stopped owing to safety concerns or lack of effectiveness.

CETP inhibitors are not only for cardiovascular illnesses but also for neurological diseases and problems connected to aging. CETP inhibitors are likely to favorably affect cognitive decline, Alzheimer's disease, and other disorders by enhancing lipid metabolism—especially raising HDL-C levels. With additional fundamental research and clinical trials underway in the future, CETP could become a significant target for many illness' therapies.

References:

Davidson MH, Hsieh A, Kastelein JJP. Cholesteryl ester transfer protein inhibition: a pathway to reducing risk of morbidity and promoting longevity. Curr Opin Lipidol. 2024;35(6):303-309.
Poliakova T, Wellington CL. Roles of peripheral lipoproteins and cholesteryl ester transfer protein in the vascular contributions to cognitive impairment and dementia. Mol Neurodegener. 2023;18(1):86.

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