Is This Detox Gene Protecting You From Pesticides? (PON1)

The PON1 gene is responsible for encoding a protein with the same name, PON1. The protein PON1, short for paraoxonase 1, is an enzyme that hydrolyzes (breaks apart) several different types of chemical bonds [R].

This ability to break down various molecules makes PON1 vital to your health. It can break apart oxidized fats that could otherwise lead to heart disease, and it can destroy certain parts of harmful bacteria. Perhaps most importantly, PON1 proteins can hydrolyze and therefore detoxify organophosphates, toxic compounds found in pesticides and biological weapons [R].

The PON1 gene encodes the PON1 protein, which protects you from toxic compounds called organophosphates.

Organophosphate Toxicity: Are You At Risk?

In the U.S., organophosphates are the most commonly used pesticides in farming. Although these pesticides are supposed to degrade when exposed to air and light, there is evidence that organophosphate residue remains on many of the fruits and vegetables we eat [R, R, R].

The widespread use of pesticides in schools, parks, and other public spaces also puts many people at risk of low-level exposure. Farm workers and military members who have been exposed to nerve agents have an even greater risk of toxicity [R].

Organophosphates are one of the most commonly used pesticides worldwide and many people are at risk for at least low-level exposure.

Health Risks of Organophosphate Toxicity

What happens when you’re exposed to organophosphates? The symptoms of acute organophosphate poisoning include fatigue, muscle weakness, and paralysis; untreated, it can eventually lead to death [R].

However, if your body isn’t properly detoxing organophosphates, even low levels of pesticide exposure can cause harmful effects, including [R, R]:

• Infertility
• Cancer
• Birth defects
• Increased risk of Alzheimer’s
• Increased risk of Parkinson’s
• Increased risk of ALS

Exposure to low levels of organophosphates may cause infertility, cancer, birth defects, and neurodegenerative disorders.

Not all PON1 protein is made equal; variations in your PON1 gene can alter the concentration and activity level of the protein. This means that some people are better protected against the toxic effects of organophosphates than others [R].

More specifically, research has identified two SNPs of the PON1 gene that influence how well your PON1 proteins protect you: rs662 and rs854560 [R].

Enzyme Activity

The SNP at rs662 influences how active the PON1 enzyme is. The normal allele “C” is associated with normal protein activity and therefore provides the best protection from toxicity. The risk allele “T” in rs662 reduces the activity of the protein, resulting in less breakdown (and more potential buildup) of toxins [R].

A large analysis of 9 studies including over 2,000 people found that people with the risk allele in rs662 have a 74% higher risk of organophosphate toxicity compared to people without it [R].

Interestingly enough, Caucasians may be at an even higher risk. According to the same study, the risk allele increases the likelihood of toxicity by up to 96% when only looking at Caucasians. On the other hand, the risk allele does not appear to affect Asian populations at all [R].

In rs662, people with the risk allele “T” have a 74% greater risk of organophosphate toxicity compared to those without it. The harmful effect of the risk allele is even greater in Caucasians but absent in Asians.

Enzyme Concentration

The concentration of PON1 protein in the blood is controlled, in part, by rs854560. In this case, the normal allele is “T” and is associated with normal PON1 levels. The risk allele “A” is associated with lower blood levels of PON1; if you have less PON1, you have a reduced ability to detox [R].

The previously mentioned analysis found that people with the risk allele “A” in rs854560 have an 82% higher risk of organophosphate toxicity compared to people without it [R].

Once again, this effect is amplified in Caucasians; their risk of toxicity jumps up by148% if they have the risk allele. Asians remain unaffected by this risk variant as well. It’s not entirely clear why risk alleles affect these two populations differently, but researchers think it may be due to environmental factors [R].

The risk allele “A” in rs854560 increases the risk of organophosphate toxicity by 82% compared to the normal “T” allele. This harmful effect is magnified in Caucasians but absent in Asians.

Primary SNPs: 

PON1 rs662

• “C” allele doesn’t increase your risk
• “T” allele increases your risk of toxicity

Population Frequency

• 24% of the world population have “TT”
• 50% of people with European ancestry have “TT”

PON1 rs854560

• “T” allele doesn’t increase your risk
• “A” allele increases your risk of toxicity

Population Frequency

• 68% of the world population have “AA”
• 41% of people with European ancestry have “AA”

Note:

• Caucasians with a risk allele have an even greater risk for toxicity compared to other groups
• Asians do not appear to be affected by the risk allele