CETP is a gene that has been the darling of medical genetics for some time. It’s latest foray into health matters is what appears to be an association between a specific variant (read allele) and a decreased incidence of Alzheimer’s Disease (AD). So before I get into the newest research, let’s take a look at the gene, what it’s protein product does, and why it’s so loved.

You may have already heard from your doctor, or even in the papers, about HDL (High Density Lipoproteins) and LDL (Low Density Lipoproteins). These are molecules in our blood made up of proteins and fat molecules (lipo, from lipids). A higher amount of HDL is associated with lower blood cholesterol, whereas a higher amount of LDL is considered unhealthy. When you do a blood test, your doctor will look at the ratio between HDL and LDL.

This is where CETP comes in. CETP is short for Cholesteryl Ester Transfer Protein, which means it has the ability to transfer bits of lipids between HDL and LDL (and also VLDL: Very Low Density Lipoproteins). When CETP levels are low, HDL levels are high. So the ideas goes, if we can inhibit CETP, we will naturally increase HDL, thus preventing heart disease. The logic is sound, but the medical benefits are still not quite clear. For instance see these two (1, 2) abstracts which were published last year.

Ok, let’s take a more detailed look at CETP itself.

Below is a typical representation of a gene on a chromosome. It’s what biologists typically look at when they want to see things other than A, C, G, and T.

The top line is the position on chromosome 16, where CETP is found. The second line shows the architecture of the gene, which is interesting, but not really the topic at the moment. The third line is really interesting. Each vertical line represents a genetic variant, a single nucleotide polymorphism (SNP) which is a change in a single letter of the genetic code. CETP is not exceptionally large, but it is sizable, and there are many SNPs within that gene, a good number of which will cause a change in the protein.

The newest information on CETP brings us such fantastic headlines as:

-‘Longevity’ Gene May Cut Dementia Risk
-Gene variant protects against Alzheimer’s: study
-Gene found that cuts chance of dementia
-‘Longevity’ gene to do more than adding years to life

Which all belie the very straight-forward title of the actual paper:

-Association of a Functional Polymorphism in the Cholesteryl Ester Transfer Protein (CETP) Gene With Memory Decline and Incidence of Dementia

What that title means is that in a group of over 500 people, 40 who went on to develop AD carried a specific SNP. It’s called functional because it leads to a change in the protein sequence that is produced from CETP. The thing to keep in mind is the abundant amount of other SNPs in the gene. Are there more specific sub-types (alleles) associated with AD? Also the sample size is quite small and so although the statistics show a significant difference in dementia incidence between different SNP carriers, further expansion of the experiment would make it clear how significant the result it. The authors make the very safe conclusion:

This preliminary report suggests that CETP V405 valine homozygosity is associated with slower memory decline and lower incident dementia and AD risk.

Which is a far cry from adding years to your life.

Image: UCSC Genome Browser

Citation:

Sanders, A., Wang, C., Katz, M., Derby, C., Barzilai, N., Ozelius, L., & Lipton, R. (2010). Association of a Functional Polymorphism in the Cholesteryl Ester Transfer Protein (CETP) Gene With Memory Decline and Incidence of Dementia JAMA: The Journal of the American Medical Association, 303 (2), 150-158 DOI: 10.1001/jama.2009.1988