PCSK9 rs11591147 (R46L): What Your DNA Result Means

Oct 2

3 min read

PCSK9 rs11591147, also called R46L, is a genetic variant associated with lower LDL cholesterol in research. It changes one building block in the PCSK9 protein, which helps regulate the LDL receptors that clear cholesterol from the blood. The association can help explain one part of inherited variation in LDL levels, but a DNA result cannot tell you your current cholesterol or predict your personal heart-disease outcome [R, R].

What Does PCSK9 Do?

LDL receptors on liver cells bind LDL particles and help remove them from the bloodstream. The PCSK9 protein helps control how many of these receptors remain available: when PCSK9 promotes receptor breakdown, fewer receptors are available to clear LDL. Some PCSK9 variants reduce this activity, leaving more receptors available and tending to lower LDL cholesterol [R].

PCSK9 variants can have different effects. Some gain-of-function variants increase PCSK9 activity and are associated with familial hypercholesterolemia, while loss-of-function variants such as R46L are associated with lower LDL. The gene name alone therefore does not indicate whether a variant raises or lowers cholesterol [R].

What Is PCSK9 rs11591147 (R46L)?

The R46L variant changes the amino acid arginine to leucine at position 46 of the PCSK9 protein. It is described as a loss-of-function variant: on average, it reduces PCSK9 activity and is associated with lower LDL cholesterol [R].

The size of the association varies between people. Other genes, age, diet, health conditions, medications, and many additional factors influence an individual’s measured LDL level.

Microscopic view of colorful protein-like spheres and shapes binding to a cell membrane in a sci-fi style scene

What Do GG, GT, and TT Results Mean?

In our free GeneExplorer tool, the R46L-associated allele is shown as T. Results are displayed as GG, GT, or TT:

Genotype	Research Interpretation
GG	No protective T allele at this SNP. This does not mean your LDL cholesterol is high.
GT	One T allele; associated with lower PCSK9 activity and lower LDL.
TT	Two T alleles; associated with lower LDL in multiple population studies.

These are associations, not a personal cholesterol reading. Genotype letters can also be presented differently across DNA tools because of strand conventions, so interpret the result in the context of the specific service reporting it.

What Have Studies Found About R46L and LDL?

A study of 103,083 people in Denmark reported median LDL cholesterol levels of 124 mg/dL for GG, 104 mg/dL for GT, and 97 mg/dL for TT [R].

In the same study, people carrying one or two T alleles had about 23% lower odds of myocardial infarction than non-carriers. The study’s participants and results cannot capture every person’s ancestry, medical history, or other risk factors [R].

What This DNA Result Can—and Cannot—Tell You

PCSK9 rs11591147 can indicate whether you carry the R46L variant and provide context about a genetic factor associated with LDL cholesterol. It cannot show your current LDL level, diagnose a cholesterol disorder, or determine whether you will develop heart disease.

A lipid blood test measures cholesterol levels in your blood. If you want to know your current LDL, discuss an appropriate lipid test and your overall risk with a healthcare professional [R]. Do not start, stop, or change medication based on a raw DNA result alone.

How PCSK9 Fits With Other Cholesterol Genes

PCSK9 is one piece of lipid biology. It affects how many LDL receptors are available to clear LDL from circulation. ApoB provides a different view of atherogenic lipoprotein particles, while CETP is involved in the transfer of cholesterol between lipoproteins. Looking at these pathways together can offer educational context, but they do not replace blood tests or a clinical assessment.

Read more about ApoB and lipoprotein particles.
Explore CETP rs5882 and cholesterol.

Frequently Asked Questions

Does the T allele in PCSK9 rs11591147 lower LDL?

The T allele is associated with reduced PCSK9 function and lower LDL cholesterol on average in population studies. It does not guarantee that an individual will have low LDL.

Does a GG result mean my cholesterol is high?

No. GG means the R46L-associated T allele was not detected at this site. It does not predict a high LDL result; a blood lipid test measures your actual cholesterol.

Does PCSK9 rs11591147 predict whether I will have a heart attack?

No. Research has found a lower average odds of myocardial infarction among carriers in a large Danish study, but this is not an individual prediction. Heart risk depends on many factors.

Can a DNA result replace a cholesterol test?

No. DNA reports an inherited variant; a lipid blood test measures cholesterol in the blood.

Explore Your PCSK9 Result

GeneExplorer includes the PCSK9 rs11591147 result. You can explore the PCSK9 R46L page or analyze your DNA for free to see which supported insights are available in your file.

GenesUnveiled provides educational information and does not diagnose or treat medical conditions.