PON1 (Paraoxonase 1) is an antioxidant enzyme that travels on HDL particles, protecting against oxidative stress and cardiovascular disease. The Q192R variant (rs662) affects enzyme activity toward different substrates, influencing both cardiovascular protection and ability to detoxify certain pesticides and toxins.
What is PON1?
Paraoxonase 1 is a calcium-dependent enzyme that:
- Prevents oxidation of LDL cholesterol (a key step in atherosclerosis)
- Protects HDL function
- Hydrolyzes organophosphate pesticides
- Breaks down certain drugs and toxins
- Has anti-inflammatory properties
PON1 is synthesized in the liver and circulates bound to HDL particles, where it exerts its protective effects.
Understanding Your Genotype
- QQ (A/A): Higher activity against oxidized lipids; lower activity against some organophosphates
- QR (A/G): Intermediate activity
- RR (G/G): Lower activity against oxidized lipids; higher activity against some organophosphates
The Q and R variants have different substrate preferences - neither is universally "better."
Cardiovascular Implications
Atherosclerosis Protection
- QQ genotype generally shows better protection against LDL oxidation
- Some studies show lower cardiovascular disease risk with QQ
- The R allele may be associated with increased coronary artery disease risk in some populations
- Effects are influenced by overall PON1 expression levels (affected by other variants and lifestyle)
HDL Quality
- PON1 contributes to HDL's cardioprotective properties
- Higher PON1 activity associated with better HDL function
- Lifestyle factors strongly influence PON1 activity regardless of genotype
Pesticide Sensitivity
PON1 detoxifies organophosphate pesticides (found in conventional agriculture):
- QQ genotype: May be more sensitive to organophosphate exposure
- RR genotype: Better at hydrolyzing some organophosphates
- Relevance for agricultural workers, gardeners, or those with high pesticide exposure
- May inform choices about organic vs. conventional produce
Supporting PON1 Activity
Dietary Factors
PON1 activity increasers:
- Moderate red wine consumption (polyphenols)
- Pomegranate juice
- Olive oil (Mediterranean diet)
- Quercetin-rich foods (onions, apples)
- Adequate vitamin C and E
PON1 activity decreasers:
- Smoking (dramatically reduces PON1)
- Excessive alcohol
- High oxidative stress states
- Chronic inflammation
Lifestyle
- Exercise increases PON1 activity
- Smoking cessation dramatically improves PON1
- Weight loss in obesity improves PON1
- Statin medications may increase PON1 activity
Prevalence
- European ancestry: Approximately 50% QQ, 40% QR, 10% RR
- African ancestry: Higher R allele frequency
- East Asian: Variable
Testing with NutraHacker
NutraHacker analyzes PON1 Q192R along with other genes affecting cardiovascular health and detoxification.
References
- Mackness MI, et al. Paraoxonase and coronary heart disease. Curr Opin Lipidol. 1998;9(4):319-324.
- Costa LG, et al. Paraoxonases as biomarkers of susceptibility to organophosphate poisoning. Clin Chim Acta. 2003;333(2):155-168.