Is This Cholesterol Gene Linked To Lifespan? (CETP)

The CETP gene codes for a protein called CETP, which stands for cholesteryl ester transfer protein. CETP is responsible for controlling the levels of cholesterol and fat in the blood, and which can help remove excess cholesterol out of the body [R].

Research has identified several genetic variants in CETP that may be associated with longevity. According to some studies, these variants may be relatively more common in people who live exceptionally long lives — although the overall evidence is still mixed, as we’ll see below [R, R].

The CETP gene codes for the CETP protein, which helps regulate cholesterol levels in the body.

Before discussing the mechanism behind CETP and its role in managing cholesterol levels, it’s important to understand a few terms [R]:

• HDL: short for high-density lipoprotein, often referred to as “good cholesterol” because it helps remove cholesterol out of the blood.
• LDL: short for low-density lipoprotein, often referred to as “bad cholesterol” because high LDL levels can cause a buildup of cholesterol in the arteries.
• Cholesteryl ester: cholesterol is converted into cholesteryl ester so that it can be transported around the body more easily.
• Triglycerides: a common type of fat in the body which is primarily used for energy.

As mentioned earlier, CETP is responsible for redistributing cholesterol in the blood. More specifically, CETP helps swap a cholesteryl ester that is attached to HDL with triglycerides that are attached to LDL. This LDL that is newly-bound to cholesteryl ester can then move to the liver, where it is eliminated from the body [R].

The CETP protein works by transferring cholesterol from HDL to LDL, where it is eventually removed from the body by the liver.

The Role Of CETP In Heart Health

Atherosclerosis is a disease that occurs when cholesterol and fat accumulate to create hard “plaque” in the blood vessels, which makes them stiffer and more prone to damage. This plaque buildup can also disrupt blood flow, and can eventually lead to increased risk of heart attacks, strokes, and other cardiovascular issues. However, there is debate on whether CETP activity actually increases or decreases the risk of atherosclerosis [R].

On the one hand, CETP activity plays a role in cholesterol removal. The elimination of excess cholesterol may be an important factor in the prevention of atherosclerosis [R, R].

On the other hand, studies show that reducing CETP activity may increase HDL and lower LDL, which are commonly regarded as ways to prevent atherosclerosis development. Reduced CETP activity may also increase the particle size of both HDL and LDL. Larger particle sizes are linked to lower rates of cardiovascular disease because they may not be able to penetrate into arterial tissue and form plaque as effectively as smaller particles [R, R, R].

Research has revealed highly conflicting results. Both CETP activity and inhibition have been associated with both increased and decreased rates of atherosclerosis and heart disease [R, R, R].

There is conflicting evidence on whether increased or decreased CETP activity is beneficial for cardiovascular health.

Certain variants in CETP are associated with longevity in some studies. According to researchers, this life-extending effect may be due to improved cholesterol levels, which may help prevent a number of heart conditions [R].

Longevity research has focused on two particular variants. The ‘GG’ genotype in rs5882 (also known as the “I405V” polymorphism) and the ‘AA’ genotype in rs708272 (also called the “TaqIB” polymorphism) have each been associated with lower CETP activity and longer lifespan [R].

However, the results of these longevity studies are not yet conclusive. In the following sections, we’ll review some of the supporting evidence, as well as the conflicting data [R, R, R].

Supporting Evidence

A study looking at 213 Ashkenazi Jews (a group that originates from Eastern Europe) revealed that the ‘GG’ genotype in rs5882 is much more common in those that live exceptionally long lives. Another study looking at Hainan Chinese also found that this ‘GG’ genotype was more prevalent in those that live past 100 years old [R, R].

Similarly, other studies of Chinese individuals from Hainan and Bama Zhuang have found that the ‘AA’ genotype in rs708272 is significantly more common in people who are 100 or more years old [R, R].

Studies have found that the ‘GG’ genotype in rs5882 and the ‘AA’ genotype in rs708272 are associated with longer lifespans in certain Jewish and Chinese populations.

Conflicting Evidence

However, there is also research that suggests that the CETP gene may have no significant effect on lifespan at all. For example, several studies have concluded that the ‘GG’ genotype in rs5882 has no association with longevity in other ethnic populations, including Japanese, Han Chinese, Danish, and Italian groups [R, R, R, R].

On top of that, a meta-analysis of 8 studies found that the ‘GG’ genotype in rs5882 may actually be associated with shorter lifespans in Han Chinese [R].

For the SNP rs708272, there is evidence suggesting that the other genotypes (‘GG’ or ‘GA’) may actually be responsible for the reported longevity effects, rather than the previously mentioned ‘AA’ genotype. On the other hand, there are also studies that suggest this SNP has no effect on longevity at all — so it’s hard to draw any firm conclusions [R, R, R].

Overall, then, it’s possible that whatever effects these SNPs might have on lifespan may depend on the specific ethnic group being studied. Therefore, more research will still be needed to figure out whether these findings apply to other groups — and in the meantime, you should keep these caveats in mind when looking at your own genotypes for CETP SNPs.

There are some studies reporting that the ‘GG’ genotype in rs5882 or the ‘AA’ genotype in rs708272 may not actually be associated with longevity after all, or may even negatively impact lifespan — and this conflicting evidence should be kept in mind when trying to interpret SNPs in this gene.

You can see your genotypes for these two SNPs in the table below. However, keep in mind that these associations are based on studies from certain ethnic populations — so you should interpret your results with caution if you are not descended from one of these specific groups!

Primary SNPs:

CETP rs5882:

• ‘A’ = No association with longevity.
• ‘G’ = More common in those with longer lifespans in certain populations.
• About 24% of people have the ‘GG’ genotype.
• The association between the ‘GG’ genotype and longevity has only been found in certain Jewish and Chinese groups.

CETP rs708272:

• ‘G’ = No association with longevity.
• ‘A’ = More common in those with longer lifespans in certain populations.
• About 15% of people have the ‘AA’ genotype.
• The association between the ‘AA’ genotype and longevity has only been found in certain Chinese populations.