What you carry at this position in your DNA and what research says about it.
Paraoxonase Enzyme Activity: 4/10 evidence, 25 publications.
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Sample genotype (not yours): G/G
Highest Paraoxonase Enzyme Activity and Optimal Lipid Profile
Having two copies of the G allele is associated with the highest levels of paraoxonase 1 enzyme activity. This optimal activity helps protect blood vessels from oxidative stress and supports healthy HDL cholesterol levels.
What this genotype means: Highest paraoxonase 1 enzyme levels; Optimized antioxidant defense; Favorable HDL cholesterol profile.
Sample genotype (not yours): A/A
Lowest Paraoxonase Enzyme Activity and Higher Cardiovascular Risk
Having two copies of the A allele leads to the lowest levels of paraoxonase 1 enzyme activity. This reduction in antioxidant defense is linked to lower HDL levels and a higher risk of cardiovascular issues.
What this genotype means: Lowest paraoxonase 1 enzyme levels; Reduced antioxidant defense; Increased risk of cardiovascular plaque buildup.
Sample genotype (not yours): G/A
Intermediate Paraoxonase Enzyme Activity and Typical Lipid Profile
Carrying one G and one A allele results in intermediate levels of the paraoxonase 1 enzyme. This profile generally provides typical cardiovascular protection and standard lipid levels.
What this genotype means: Intermediate paraoxonase 1 enzyme levels; Typical antioxidant defense; Standard lipid levels.
Gene function and biological role
Gene Function: The PON1 gene encodes paraoxonase 1, an enzyme primarily synthesized in the liver and secreted into the bloodstream, where it associates with high-density lipoprotein particles [1]. This enzyme plays a vital role in protecting low-density and high-density lipoproteins from oxidative damage, which is a key step in preventing plaque buildup in the arteries [2]. Beyond its cardiovascular protective properties, the enzyme is well-known for its ability to hydrolyze and detoxify organophosphate pesticides and other toxic chemicals [3]. It also acts on endogenous substrates like homocysteine thiolactone, helping clear reactive metabolites that can damage blood vessels [1].
Variant Impact: The rs705379 variant, located in the promoter region of the PON1 gene, directly influences how much of the paraoxonase 1 enzyme the body produces [2]. Often referred to in scientific literature as the -108C/T polymorphism, this genetic change alters the binding efficiency of transcription factors, thereby regulating gene expression [2]. The G allele drives higher promoter activity, resulting in significantly elevated levels of circulating enzyme [2]. Conversely, the A allele reduces promoter activity, leading to lower enzyme levels and decreased antioxidant capacity [2]. This variation has wide-ranging effects on lipid profiles, cardiovascular health, and the body's ability to neutralize environmental toxins [4].
Key Insight: This variant is located in the gene's promoter region, meaning it acts like a volume dial controlling how much antioxidant enzyme your liver actually produces.
Location: PON1. Chromosome 7 · 7q21.3 · 95.3 Mb
Estimated prevalence by population
Global 41.4%; European 27.0%; African 74.3%; East Asian 30.9%; South Asian 35.9%; Americas 27.9%; Ashkenazi 14.7%; Finnish 42.7%; Middle Eastern 22.6%; Amish 45.9%.
Estimated GG genotype frequency.
Global 42.2%; European 49.9%; African 23.8%; East Asian 49.4%; South Asian 48.0%; Americas 49.8%; Ashkenazi 47.3%; Finnish 45.3%; Middle Eastern 49.9%; Amish 43.7%.
Estimated GA genotype frequency.
Global 16.3%; European 23.1%; African 1.9%; East Asian 19.7%; South Asian 16.1%; Americas 22.3%; Ashkenazi 37.9%; Finnish 12.0%; Middle Eastern 27.5%; Amish 10.4%.
Estimated AA genotype frequency.
Showing effects for G/G genotype
Cardiovascular & Metabolic
Lipids & Cholesterol
Paraoxonase Activity. Evidence: 4/10. Source: PMID 24448003. Highest Activity.
HDL Cholesterol. Evidence: 10/10. Source: PMID 34887591. Higher Levels.
Heart Disease
Cardiovascular Risk. Evidence: 4/10. Source: PMID 22388798. Lower Risk.
Organ Systems
Vision & Eye Health
Macular Degeneration. Evidence: 3/10. Source: PMID 22956172. Lower Risk.
Pharmacogenomics
Immunosuppressant & Biologic Response
Leflunomide Response. Evidence: 5/10. Source: PMID 40183079. Stronger Response.
Showing effects for A/A genotype
Paraoxonase Activity. Evidence: 4/10. Source: PMID 24448003. Lowest Activity.
HDL Cholesterol. Evidence: 10/10. Source: PMID 34887591. Lower Levels.
Cardiovascular Risk. Evidence: 4/10. Source: PMID 22388798. Higher Risk.
Macular Degeneration. Evidence: 3/10. Source: PMID 22956172. Higher Risk.
Leflunomide Response. Evidence: 5/10. Source: PMID 40183079. Reduced Response.
Showing effects for G/A genotype
Paraoxonase Activity. Evidence: 4/10. Source: PMID 24448003. Intermediate.
HDL Cholesterol. Evidence: 10/10. Source: PMID 34887591. Typical Levels.
Cardiovascular Risk. Evidence: 4/10. Source: PMID 22388798. Typical Risk.
Macular Degeneration. Evidence: 3/10. Source: PMID 22956172. Typical Risk.
Leflunomide Response. Evidence: 5/10. Source: PMID 40183079. Typical Response.
What this genotype means for the people who carry it
Sample genotype: GG (Homozygous)
Circulating levels of the paraoxonase 1 enzyme reach their peak in those with this specific genetic profile [1]. Higher enzyme levels translate to robust arylesterase activity, which is crucial for preventing the oxidation of LDL cholesterol [1]. This protective mechanism helps maintain healthy blood vessels and lowers the long-term risk of developing cardiovascular complications [2]. Genetic studies show a strong association between this genotype and increased HDL cholesterol levels, as well as larger, more protective HDL particle sizes [3]. Furthermore, the abundant enzyme levels provide an enhanced capacity to detoxify organophosphate pesticides and other environmental chemicals [4]. Individuals with this profile also show a more favorable response to certain medications, such as leflunomide used in rheumatoid arthritis treatment [5]. Overall, this genetic makeup offers a strong natural defense against oxidative cardiovascular damage and environmental toxins.
Highest paraoxonase 1 enzyme levels; Optimized antioxidant defense; Favorable HDL cholesterol profile.
Sample genotype: AA (Homozygous)
Production of the protective paraoxonase 1 enzyme is significantly reduced in individuals with this genetic profile [1]. This low promoter activity results in the lowest levels of circulating arylesterase, leaving blood vessels more vulnerable to oxidative damage [1]. Over time, this lack of antioxidant defense can contribute to an increased risk of coronary artery disease and other cardiovascular issues [2]. Lipid profiles typically show lower HDL cholesterol levels and smaller HDL particle sizes, which are less effective at clearing cholesterol from the arteries [3]. There is also an associated increase in the risk of neovascular age-related macular degeneration due to heightened oxidative stress in retinal tissues [4]. Furthermore, the reduced enzyme levels compromise the body's ability to efficiently detoxify organophosphate pesticides, making environmental exposure more impactful [5]. Maintaining a heart-healthy diet rich in antioxidants and avoiding pesticide exposure are particularly beneficial strategies for individuals with this profile.
Lowest paraoxonase 1 enzyme levels; Reduced antioxidant defense; Increased risk of cardiovascular plaque buildup.
Sample genotype: GA (Heterozygous)
Enzyme production falls into a moderate, intermediate range for individuals carrying this combination of alleles [1]. While the single G allele provides a baseline level of antioxidant protection, the presence of the A allele slightly tempers overall promoter activity [1]. Consequently, the body maintains a typical lipid profile, with average HDL cholesterol levels and standard HDL particle sizes [2]. Cardiovascular risk and susceptibility to oxidative stress remain at baseline, average levels for the general population [3]. The capacity to neutralize organophosphate pesticides and clear reactive metabolic byproducts is also intermediate, offering moderate protection [4]. Response rates to medications like leflunomide are typical, falling between the high-response and low-response groups [5]. This balanced genetic profile represents the most common baseline in many populations, requiring no special interventions beyond standard healthy lifestyle choices.
Intermediate paraoxonase 1 enzyme levels; Typical antioxidant defense; Standard lipid levels.
Variants with shared genetic architecture
rs662 · PON1 Gene · Chr 7 · Heart Disease Risk
rs854560 · PON1 Gene · Chr 7 · Cardiovascular Health
rs854572 · PON1 Gene · Chr 7 · Antioxidant Protection
Childhood brain tumors, residential insecticide exposure, and pesticide metabolism genes.
The power of genetic diversity in genome-wide association studies of lipids.
Content updated August 2026.
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