What you carry at this position in your DNA and what research says about it.
Heart Disease Risk: 5/10 evidence, 65 publications.
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Sample genotype (not yours): T/T
Lower Heart Disease Risk but Slower Chemical Detoxification
Glutamine-containing paraoxonase 1 enzymes are produced by this genotype, offering robust protection against arterial plaque buildup.
What this genotype means: Lower risk of coronary artery disease; Slower detoxification of organophosphate pesticides; Potentially reduced activation of clopidogrel.
Sample genotype (not yours): C/C
Higher Heart Disease Risk but Faster Chemical Detoxification
Arginine-containing paraoxonase 1 enzymes are produced by this genotype, which reduces antioxidant protection in the arteries but speeds up pesticide clearance.
What this genotype means: Increased risk of coronary artery disease; Fastest detoxification of organophosphate pesticides; Enhanced HDL-cholesterol response to simvastatin.
Sample genotype (not yours): T/C
Slightly Higher Heart Disease Risk and Moderate Chemical Detoxification
An intermediate level of paraoxonase 1 enzyme activity characterizes this genotype, resulting in a slightly increased risk of coronary artery disease.
What this genotype means: Slightly increased risk of coronary artery disease; Moderate detoxification of organophosphate pesticides; Typical response to statin therapy.
Gene function and biological role
Gene Function: The PON1 gene encodes paraoxonase 1, an enzyme produced in the liver and carried through the bloodstream on high-density lipoprotein HDL particles [1]. This enzyme plays a vital role in cardiovascular health by preventing the oxidation of low-density lipoprotein LDL cholesterol, a key process that triggers plaque buildup in the arteries [2]. Additionally, paraoxonase 1 acts as a detoxifying agent, breaking down harmful organophosphate pesticides, nerve agents, and environmental toxins [3]. It also processes certain medications, including antiplatelet drugs like clopidogrel and statins like simvastatin [4].
Variant Impact: The rs662 variant, commonly known as Q192R, is a missense mutation that changes the 192nd amino acid of the paraoxonase 1 enzyme from glutamine to arginine [1]. This single-letter change alters the enzyme's physical shape, modifying how tightly it binds to HDL particles and changing its catalytic efficiency [1]. The reference T allele encodes glutamine, which provides superior antioxidant protection against LDL oxidation [2]. Conversely, the variant C allele encodes arginine, which increases the enzyme's ability to hydrolyze certain chemical toxins but reduces its capacity to prevent lipid oxidation [3].
Key Insight: The same genetic variant that increases heart disease risk actually makes the body more efficient at neutralizing toxic organophosphate pesticides and chemical nerve agents.
Location: PON1. Chromosome 7 · 7q21.3 · 95.3 Mb
Estimated prevalence by population
Global 36.4%; European 51.6%; African 10.9%; East Asian 12.8%; South Asian 37.3%; Americas 33.2%; Ashkenazi 45.9%; Finnish 50.0%; Middle Eastern 44.0%; Amish 44.8%.
Estimated TT genotype frequency.
Global 43.0%; European 40.5%; African 44.2%; East Asian 46.0%; South Asian 47.6%; Americas 48.8%; Ashkenazi 43.7%; Finnish 41.4%; Middle Eastern 44.7%; Amish 44.3%.
Estimated TC genotype frequency.
Global 20.7%; European 7.9%; African 44.9%; East Asian 41.2%; South Asian 15.2%; Americas 17.9%; Ashkenazi 10.4%; Finnish 8.6%; Middle Eastern 11.3%; Amish 10.9%.
Estimated CC genotype frequency.
Showing effects for T/T genotype
Cardiovascular & Metabolic
Heart Disease
Heart Disease. Evidence: 4/10. Source: PMID 24918121. Lower Risk.
Pharmacogenomics
Drug Metabolism Enzyme Activity
Pesticide Sensitivity. Evidence: 3/10. Source: PMID 7916578. Slower Clearance.
Lipid-Lowering Drug Response
Statin Response. Evidence: 5/10. Source: PMID 18430057. Typical Response.
Anticoagulant & Blood Thinner Response
Clopidogrel Response. Evidence: 5/10. Source: PMID 21170047. Reduced Response.
Showing effects for C/C genotype
Heart Disease. Evidence: 4/10. Source: PMID 24918121. Higher Risk.
Pesticide Sensitivity. Evidence: 3/10. Source: PMID 7916578. Fastest Clearance.
Statin Response. Evidence: 5/10. Source: PMID 18430057. Better HDL Response.
Clopidogrel Response. Evidence: 5/10. Source: PMID 21170047. Typical Response.
Showing effects for T/C genotype
Heart Disease. Evidence: 4/10. Source: PMID 24918121. Slightly Higher Risk.
Pesticide Sensitivity. Evidence: 3/10. Source: PMID 7916578. Faster Clearance.
Clopidogrel Response. Evidence: 5/10. Source: PMID 21170047. Intermediate Response.
What this genotype means for the people who carry it
Sample genotype: TT (Homozygous)
The presence of two T alleles produces the glutamine-containing form of the paraoxonase 1 enzyme [1]. This specific enzyme form binds stably to HDL particles, providing robust antioxidant defense that prevents LDL cholesterol from oxidizing and forming arterial plaques [2]. Consequently, multiple clinical studies have linked this genotype to a lower risk of coronary artery disease and subclinical atherosclerosis [3]. However, this version of the enzyme is less efficient at breaking down organophosphate pesticides and chemical nerve agents [4]. Additionally, some early research suggested that individuals with this genotype might have a reduced response to the blood thinner clopidogrel, although larger clinical trials have shown conflicting results regarding its overall impact on cardiovascular events [5].
Lower risk of coronary artery disease; Slower detoxification of organophosphate pesticides; Potentially reduced activation of clopidogrel.
Sample genotype: CC (Homozygous)
Possessing two copies of the C allele encodes the arginine-containing form of the paraoxonase 1 enzyme [1]. This version of the enzyme has a lower affinity for HDL particles and is less effective at preventing the oxidation of LDL cholesterol, which can accelerate plaque buildup in the arteries [2]. As a result, several studies have linked this genotype to an increased risk of coronary artery disease and ischemic stroke [3]. Conversely, the arginine-containing enzyme is highly efficient at hydrolyzing and neutralizing organophosphate pesticides and chemical toxins, offering superior protection against these specific environmental exposures [4]. Furthermore, individuals with this genotype have been shown to experience a significantly better HDL-cholesterol response when treated with the statin simvastatin [5].
Increased risk of coronary artery disease; Fastest detoxification of organophosphate pesticides; Enhanced HDL-cholesterol response to simvastatin.
Sample genotype: TC (Heterozygous)
A combination of one T allele and one C allele leads to a mixture of both glutamine- and arginine-containing paraoxonase 1 enzymes in the bloodstream [1]. Because the arginine-containing enzyme is less effective at preventing LDL cholesterol oxidation, this genotype is associated with a slightly higher risk of coronary artery disease and plaque buildup than the T/T genotype [2]. On the positive side, having one C allele provides a moderate increase in the ability to break down and detoxify organophosphate pesticides and environmental toxins compared to those with the T/T genotype [3]. In terms of medication response, some studies suggest a typical response to statins like simvastatin, while the clinical impact on clopidogrel responsiveness remains highly debated with mixed findings across different populations [4].
Slightly increased risk of coronary artery disease; Moderate detoxification of organophosphate pesticides; Typical response to statin therapy.
Variants with shared genetic architecture
rs854560 · PON1 Gene · Chr 7 · Cardiovascular Health
rs854572 · PON1 Gene · Chr 7 · Antioxidant Protection
rs705379 · PON1 Gene · Chr 7 · Paraoxonase Enzyme Activity
The molecular basis of the human serum paraoxonase activity polymorphism.
Association between PON1 rs662 polymorphism and coronary artery disease.
Content updated August 2026.
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