How Genes Influence Chemical Sensitivity?

Our quick and acute response to certain environmental stimuli can pose health issues due to our subjective sensitivity.

Exposure to environmental chemicals (including cleaning products, detergents, diesel exhaust, formaldehyde, plastics, carpets, epoxy, pesticides, and synthetic/ natural fragrances) can cause chemical sensitivity in some people even at doses far below those usually harmful to most others.

Chemical sensitivity is both different and similar to an allergic reaction.

What Is Chemical Sensitivity And What Are Its Symptoms?

Chemical Sensitivity (CS), also known as Multiple Chemical Sensitivity (MCS), Chemical Intolerance (CI), Idiopathic Environmental Illness (IEI), or Toxicant Induced Loss of Tolerance (TILT), is an acquired multifactorial syndrome.

It is characterized by a recurrent set of debilitating symptoms, including:

Perceived hypersensitivity to the smell of chemicals
Nausea
Dizziness
Headache
Fatigue
Runny eyes
Chest and throat pain
Dyspepsia (indigestion or discomfort in the upper abdomen, often after eating or drinking)
Arthralgia (a discomfort, pain, or inflammation in joints)
Lack of concentration
Memory difficulties
Depression
Anxiety
Mood disruption.

These symptoms involve a large spectrum of organ systems and typically disappear when the sensitivity-causing environmental chemicals are removed.

Physiological Changes That We Undergo During Chemical Sensitivity

Chemical sensitivity is an acquired disorder in which a specific set of diagnosable medical conditions involving the respiratory, cardiac, gastrointestinal, musculoskeletal, dermal, and nervous systems are exacerbated by exposure to chemicals found in the environment at levels that neither produce acute toxicity nor affect most individuals.

Chemical sensitivity occurs due to amplified immune responses triggered by c-fibers or an altered function in the respiratory epithelium.

Odorous (foul-smelling) chemicals, for instance, trigger the responses of unmyelinated c-fiber neurons, which are widely distributed in the mucous covering the respiratory tract.

This, in turn, results in the release of substance P, a key element of many inflammatory processes.

The consequent immune response then suggestively provokes central nervous system (CNS)-mediated symptoms such as emesis, nausea, mood disorders, and stress4.

Thus, it is clear that chemical stimulation at one body site, for example, the mucous membrane of the nose, can lead to inflammation in other distant sites, thereby provoking symptoms like headache or tachycardia (increased heart rate).

Allergic responses and alterations in the immune system have been proposed as a possible etiological mechanism of chemical sensitivity.

Toxicants such as pesticides, solvents, and various hydrocarbons can reach the brain through the respiratory passage.

Many individuals with chemical sensitivity have rosacea with erythema and inflammation of the face.

Airborne contact dermatitis is the skin inflammation produced by exposure to chemicals in the air.

Genetics and Chemical Sensitivity

A certain degree of genetic variability exists amongst us, which is a major contributor to deciding who is more susceptible to chemical sensitivities.

One concept is that people with chemical sensitivity have fewer or less effective enzymes for detoxifying chemicals and metabolizing drugs.

This could make them more prone to developing the associated symptoms.

For instance, individuals with hereditary blood disorders like sickle cell anemia are sensitive to benzene, cadmium, and lead, aggravating their anemia symptoms.

Likewise, deficiencies in serum alpha-1-antitrypsin can leave individuals susceptible to lung diseases from sensitivity to air pollutants such as ozone because of genetic reasons.

Genes and Benzene Sensitivity

Benzene, a group I carcinogen (cancer-causing agent), is commonly used to synthesize organic chemicals and is an important component of many organic solvents.

Daily-use products containing benzene include adhesives, glues, kerosene, cigarette lighter fluid, detergents, gasoline, paints, vinyl thinner, and pesticides.

Exposure to benzene can occur by inhaling fumes or vapors of benzene-containing products or by getting benzene on one’s skin.

Workers exposed to benzene may potentially suffer chronic benzene poisoning (BP).

Clinical reports have shown that exposure to benzene can result in a variety of blood and bone marrow disorders, including leukopenia, anemia, myelodysplastic syndrome, aplastic anemia, acute myeloid leukemia, and acute lymphocytic leukemia.

Metabolic enzymes involved in benzene activation or detoxification include NAD(P)H, quinone oxidoreductase 1 (NQO1), cytochrome P450 2E1 (CYP2E1), myeloperoxidase (MPO), glutathione-S-transferase mu-1 (GSTM1), and glutathione-S-transferase theta-1 (GSTT1).

Unfavorable changes in genes that provide instructions to produce these metabolic enzymes can increase the susceptibility to benzene hypersensitivity.

For example, NQO1 is an enzyme that prevents the production of free oxygen radicals, thus protecting the cell from oxidative stress.

A variation in this gene, rs1800566, might result in lowered NQO1 enzyme activity, and thus ‘TT’ genotypes or individuals carrying the mutant allele are susceptible to benzene hemotoxicity.

Interestingly, individuals carrying NQO1 rs1800566 TT genotype hike their risk for benzene poisoning if they are in the habit of smoking or drinking.

Genes and Arsenic Sensitivity

Many commonly consumed foods, including rice and shellfish, contain arsenic and heavy metal in traces, which doesn't impact health significantly.

However, chronic exposure to arsenic through food and drinking water at colossal doses is a serious global health issue.

Arsenic can increase the risk for cancer, cardiorespiratory diseases, and other chronic conditions.

After ingestion, arsenic gets absorbed into the bloodstream and is metabolized to facilitate its excretion via urine.

The metabolism of such chemicals is influenced by a person's genetic makeup.

The FTCD gene (formiminotransferase cyclodeaminase) is associated with arsenic metabolism efficiency and risk for arsenic-induced skin lesions.

It provides instructions for the production of the FTCD enzyme, which is expressed predominantly in the liver.

The FTCD enzyme catalyzes the two chemical reactions that are crucial in lowering blood arsenic concentrations and removing arsenic from the body.

A genetic change (single nucleotide polymorphism/SNP) in the FTCD gene at rs61735836 results in reduced urinary arsenic elimination in individuals carrying the 'AA' genotype.

This genotype also increases skin lesion risk in its carriers owing to arsenic sensitivity.

Genes and Lead Sensitivity

We are all fond of candy, aren't we?

But did you know that the ink from plastic or paper candy wrappers may contain lead (a toxic, heavy metal) that leaches or seeps into the candy?

Not just this, lead may accidentally get into food products, medicines, or cosmetics during packaging.

Consuming even small amounts of lead can be harmful, and lead poisoning from these items can cause detrimental health effects.

Occupational risk for lead poisoning wraps up individuals employed in battery manufacturing, smelting, and mining.

Variation in lead absorption may be linked to genetic factors that influence mineral metabolism.

The vitamin D receptor (VDR) gene influences vitamin D levels in the body and thus plays a role in calcium metabolism and bone health.

This gene affects lead absorption from the gastrointestinal tract and may affect lead storage or release from bone, probably because of lead's chemical similarity with calcium.

A change in the VDR gene (rs7975232) makes its 'T' allele carriers more susceptible to lead poisoning.

Genes and Mercury Sensitivity

Mercury poisoning is a type of metal poisoning occurring because of overexposure to mercury.

Mercury is a naturally occurring metal that exists in many everyday products, albeit in tiny amounts.

While this limited exposure is usually considered safe, a buildup of mercury is highly dangerous.

Seafood consumption and dental fillings are the widespread origins of mercury poisoning.

The protein produced by the ABCC2 gene is a member of the superfamily of ATP-binding cassette (ABC) transporters.

ABC proteins transport various molecules across cells; renal mercury export or mercury elimination from the body is a crucial process taken up by this gene.

A change in this gene at rs1885301 causes higher neurotoxic potential in its 'A' allele carriers.

Genes and Trichloroethylene (TCE) Sensitivity

TCE is an industrial chemical that has been identified with neurotoxicity, hepatotoxicity, kidney toxicity, and immunotoxicity.

TCE-induced hypersensitivity syndrome is a dose-independent and potentially life-threatening disease that has become a serious occupational health issue.

TCE is a widely used industrial solvent. Consumer products that contain TCE include typewriter correction fluids, paint removers/strippers, adhesives, stain removers, and rug-cleaning fluids.

TCE-induced hypersensitivity syndrome may be due to T-cell-mediated immune diseases.

Several genetic factors, including HLA background, immune cytokine, and chemokines and cell surface receptor polymorphisms, are involved.

The C allele of rs2857281 in the MICA (Major Histocompatibility Complex Class I Chain-Related Protein A) gene is associated with Trichloroethylene-induced Hypersensitivity.

How To Reduce Your Exposure To Dangerous Chemicals

At Home

Cleaning Products

Most cleaning products give out fumes, which, when inhaled, can be very dangerous.

Masking yourself well while using the cleaning products and keeping the cleaning area ventilated can minimize exposure to these fumes.

Heaters and Burners

A kerosene heater, when poorly maintained, can release carbon monoxide, carbon dioxide, and soot.

Keep the area around the heater well ventilated and maintain it well to avoid the leak of these gases.

Garden/Yard Work

When the soil is riddled with pesticides, it can enter your system through the food grown in the garden, the skin when working with the soil, and breathing polluted soil as dust particles.

Checking the soil quality now and then, using limited amounts of pesticides, and dampening the soil before you garden can help protect yourself from the chemicals present in the pesticides.

At Work

Workplace exposure can happen in factories, chemical plants, manufacturing, and automobile shops.

Gearing up adequately and changing and washing your clothes before leaving your workplace can help reduce your exposure.

At Play

If your hobbies involve pottery, woodwork, and painting, you may be at risk for overexposure to chemicals.

Keeping the play area well ventilated, washing your hands with soap and water, using the chemicals with the utmost caution (after reading the instruction manual), and wearing protective gear like gloves and masks can all help with reducing your exposure chance.

Summary

In our everyday life, we get exposed to a lot of chemicals via food, pollution, cosmetics, cleaning products, and the workplace environment.
Our body has a good detoxification process set up to break down and excrete all these chemicals.
In some people, the genes involved in the detoxification process have a few changes that affect the enzyme activities. As a result, in such people, the chemicals get built up.
Overexposure to and under clearance of these chemicals can lead to dangerous health conditions like heart diseases and cancer.
Taking certain precautions at home, work, and play while dealing with chemicals can help avoid overexposure to them.