What you carry at this position in your DNA and what research says about it.
Heart Disease Risk: 10/10 evidence, 69 publications.
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Sample genotype (not yours): G/G
Typical Heart Disease Risk
Two copies of the common G allele are associated with typical levels of LDL cholesterol and a standard risk of cardiovascular disease.
What this genotype means: Typical LDL cholesterol levels; Standard lifetime risk of heart disease; Typical response to statin therapy.
Sample genotype (not yours): G/T
Significantly Lower Heart Disease Risk
One copy of the T allele is linked to naturally lower LDL cholesterol levels and a substantial reduction in the lifetime risk of heart disease.
What this genotype means: Naturally lower LDL cholesterol; Significantly reduced risk of heart attacks; Slightly increased risk of osteoarthritis.
Sample genotype (not yours): T/T
Two copies of the rare T allele are associated with exceptionally low LDL cholesterol levels and a major reduction in cardiovascular risk.
What this genotype means: Exceptionally low LDL cholesterol; Highly reduced risk of coronary artery disease; Slightly increased risk of osteoarthritis.
Gene function and biological role
Gene Function: The PCSK9 gene encodes a protein that plays a critical role in regulating cholesterol levels in the blood. It does this by binding to low-density lipoprotein receptors on the surface of liver cells, promoting their breakdown [1]. Fewer receptors on liver cells mean less LDL cholesterol is cleared from the bloodstream, leading to higher circulating levels [1]. Genetic variations that reduce PCSK9 activity allow more receptors to remain active, significantly lowering LDL cholesterol [2]. This gene has become a major target for cholesterol-lowering medications, including PCSK9 inhibitors [2].
Variant Impact: Replacing arginine with leucine at position 46 of the PCSK9 protein creates a highly beneficial loss-of-function change. This molecular alteration, known as R46L, makes the PCSK9 protein less effective at destroying LDL receptors in the liver [1]. Consequently, more LDL receptors remain on the surface of liver cells to clear LDL cholesterol from the blood [1]. This leads to lifelong, significantly lower levels of circulating LDL cholesterol [2]. Because of this natural lipid-lowering effect, carriers of this variant enjoy a highly reduced risk of cardiovascular disease [2].
Key Insight: Carrying this variant mimics the effect of modern, high-tech cholesterol-lowering drugs called PCSK9 inhibitors, providing a natural, lifelong shield against heart disease.
Location: PCSK9. Chromosome 1 · 1p32.3 · 55.0 Mb
Estimated prevalence by population
Global 97.6%; European 96.8%; African 99.5%; East Asian 100.0%; South Asian 99.8%; Americas 98.3%; Ashkenazi 99.1%; Finnish 91.4%; Middle Eastern 100.0%; Amish 98.7%.
Estimated GG genotype frequency.
Global 2.4%; European 3.2%; African 0.5%; East Asian 0.0%; South Asian 0.2%; Americas 1.7%; Ashkenazi 0.9%; Finnish 8.4%; Middle Eastern 0.0%; Amish 1.3%.
Estimated GT genotype frequency.
Global < 0.1%; European < 0.1%; African < 0.1%; East Asian 0.0%; South Asian < 0.1%; Americas < 0.1%; Ashkenazi < 0.1%; Finnish 0.2%; Middle Eastern 0.0%; Amish < 0.1%.
Estimated TT genotype frequency.
Showing effects for G/G genotype
Cardiovascular & Metabolic
Lipids & Cholesterol
LDL Cholesterol. Evidence: 10/10. Source: PMID 18193044. Typical.
Total Cholesterol. Evidence: 10/10. Source: PMID 28270201. Typical.
Heart Disease
Coronary Artery Disease. Evidence: 10/10. Source: PMID 28714975. Typical Risk.
Heart Attack. Evidence: 10/10. Source: PMID 33532862. Typical Risk.
Vascular Health & Aneurysm
Aortic Aneurysm. Evidence: 8/10. Source: PMID 32981348. Typical Risk.
Organ Systems
Bone, Joint & Connective Tissue Health
Osteoarthritis. Evidence: 4/10. Source: PMID 29436472. Typical Risk.
Pharmacogenomics
Lipid-Lowering Drug Response
Statin Response. Evidence: 10/10. Source: PMID 26902539. Typical Response.
Showing effects for G/T genotype
LDL Cholesterol. Evidence: 10/10. Source: PMID 18193044. ~15% Lower.
Total Cholesterol. Evidence: 10/10. Source: PMID 28270201. Lower.
Coronary Artery Disease. Evidence: 10/10. Source: PMID 28714975. 2-3 Fold Lower Risk.
Heart Attack. Evidence: 10/10. Source: PMID 33532862. Lower Risk.
Aortic Aneurysm. Evidence: 8/10. Source: PMID 32981348. Lower Risk.
Osteoarthritis. Evidence: 4/10. Source: PMID 29436472. Slightly Higher Risk.
Statin Response. Evidence: 10/10. Source: PMID 26902539. Stronger Response.
Showing effects for T/T genotype
LDL Cholesterol. Evidence: 10/10. Source: PMID 18193044. ~30% Lower.
What this genotype means for the people who carry it
Sample genotype: GG (Homozygous)
Cholesterol metabolism in this profile follows the standard baseline pathway. Without the protective leucine-producing T allele, the PCSK9 protein functions at normal capacity, regulating LDL receptors in a standard manner [1]. Consequently, circulating LDL cholesterol and total cholesterol levels remain in the typical range for your demographic [2]. This translates to a standard, average lifetime risk of developing coronary artery disease or experiencing a heart attack [3]. While this profile does not offer the genetic shield against cardiovascular issues seen in T allele carriers, it also does not carry the slightly elevated risk of osteoarthritis associated with that variant [4]. Maintaining healthy cholesterol levels through diet, exercise, and standard medical care remains the primary strategy for cardiovascular health. Regular lipid panels can help monitor these levels over time to ensure they stay within a safe range.
Typical LDL cholesterol levels; Standard lifetime risk of heart disease; Typical response to statin therapy.
Sample genotype: GT (Heterozygous)
Cardiovascular health is highly optimized in this profile due to a single copy of the protective T allele. This genetic change reduces the activity of the PCSK9 protein, allowing more LDL receptors to remain active on liver cells and clear cholesterol from the blood [1]. As a result, circulating LDL cholesterol levels are typically reduced by about fifteen percent from an early age [2]. This lifelong reduction in cholesterol translates to a dramatic two- to three-fold lower risk of coronary artery disease and heart attacks [3]. Additionally, research suggests that individuals with this profile may respond even better to cholesterol-lowering statin therapies if they ever need them [4]. However, there is a minor trade-off, as some studies associate this variant with a slightly higher risk of osteoarthritis [5]. Overall, this profile represents a powerful natural defense against heart disease.
Naturally lower LDL cholesterol; Significantly reduced risk of heart attacks; Slightly increased risk of osteoarthritis.
Sample genotype: TT (Homozygous)
Maximum genetic protection against high cholesterol is achieved with this rare profile. With two copies of the T allele, PCSK9 protein activity is significantly minimized, leading to an abundance of active LDL receptors on liver cells [1]. This allows the liver to highly efficiently clear LDL cholesterol from the bloodstream, resulting in very low circulating levels [2]. The lifelong exposure to low cholesterol levels provides a powerful shield, reducing the risk of coronary artery disease and heart attacks by two- to three-fold [3]. Individuals with this profile also tend to show an excellent response to statin medications if prescribed [4]. While there is a potential minor increase in the risk of osteoarthritis, the cardiovascular benefits of this genotype are profound [5]. This profile is exceptionally rare outside of certain European populations, particularly in Finland. It serves as a remarkable example of how a single genetic change can dramatically alter disease susceptibility.
Exceptionally low LDL cholesterol; Highly reduced risk of coronary artery disease; Slightly increased risk of osteoarthritis.
Variants with shared genetic architecture
rs2479409 · PCSK9 Gene · Chr 1 · Cholesterol Levels
rs28362286 · PCSK9 Gene · Chr 1 · LDL Cholesterol Levels
rs11206510 · PCSK9 Gene · Chr 1 · Heart Disease Risk
Effect of mutations in the PCSK9 gene on the cell surface LDL receptors.
A novel variant in GLIS3 is associated with osteoarthritis.
The effect of genetic variation in PCSK9 on the LDL-cholesterol response to statin therapy.
Content updated August 2026.
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