respiratory health

CYP1A1

Can This Gene Increase the Risk of Pneumonia and ARDS? (CYP1A1)

Written by Biljana Novkovic, PhD on April 10th, 2020

Can your version of the CYP1A1 gene make you more susceptible to pneumonia and ARDS (acute respiratory distress syndrome)? Studies of CYP1A1 suggest that may be the case. Read on to learn more!

What is CYP1A1?

CYP1A1 belongs to a group of enzymes called CYP enzymes. CYP enzymes help eliminate toxins from the human body. Unlike other CYP enzymes, which are mostly found in the liver, CYP1A1 is mainly found in the lungs [R, R, R].

CYP1A1’s main task is to help remove toxins that are released from burning coal, oil, gasoline, trash, tobacco, wood, or charcoal-broiled meat (polycyclic aromatic hydrocarbons, or just “PAHs” for short) [R].

In addition, there are studies that suggest that CYP1A1 may also protect against oxidative stress, by neutralizing reactive oxygen species (ROS) in the lungs [R].

CYP1A1 is an enzyme that helps remove toxic chemicals from the lungs.

CYP1A1, Pneumonia, and ARDS

Why do people respond differently to respiratory infections? While some are barely affected, others can develop serious symptoms and complications, such as pneumonia. In part, this is often due to underlying diseases and immune issues. But scientists think that genetics also plays a role.

A group of Russian scientists has found that the ‘A’ allele of rs2606345, a SNP in the CYP1A1 gene, was associated with increased susceptibility to pneumonia (3 studies each with several hundred people) [R, R, R].

Furthermore, in another study of 750 people, those with pneumonia who had the ‘AA’ genotype had a higher risk of acute respiratory distress syndrome (ARDS) [R].

ARDS is a progressive, life-threatening condition that may develop from severe cases of respiratory diseases such pneumonia. During ARDS, the lungs no longer work properly because they get filled with fluid leaking from the blood vessels. This leads to labored breathing, insufficient oxygen supply, and eventually organ failure. People with ARDS often need to go on a ventilator, and over 40% of them end up dying [R, R, R, R, R].

A variant in CYP1A1 is more common in those with pneumonia and was associated with a higher risk of developing ARDS, an often fatal complication of respiratory diseases such as pneumonia.

Potential Mechanisms

Studies suggest that the ‘A’ allele of rs2606345 decreases CYP1A1 levels [R]. Scientists currently believe that lower CYP1A may contribute to lung inflammation in pneumonia, although the exact mechanisms are still unknown [R, R].

A potential explanation is that CYP1A1 may protect against reactive oxygen species (ROS).

Mice without CYP1A1 experience more lung damage and inflammation due to oxidative stress and reactive oxidative species (ROS) [R].

Interestingly, female mice do better when exposed to oxidative stress (due to excess oxygen) because they have higher CYP1A1 levels [R].

A study in humans suggests that women have higher levels of CYP1A1 compared to men in general, but we don’t know how this relates to the rs2606345 SNP [R].

Variants that decrease CYP1A1 enzyme levels may contribute to inflammation in pneumonia by making the lungs more vulnerable to oxidative stress. Men tend to have lower CYP1A1 levels than women.

Your CYP1A1 Results for Pneumonia / ARDS

Note that our knowledge of human CYP1A1 variants in pneumonia comes from a single laboratory, and needs independent verification.

SNP Table

variant	genotype	frequency	risk allele
rs2606345

CYP1A1 rs2606345:

‘C’ = the most common allele; associated with higher CYP1A1 expression [R]
‘A’ = the relatively less common allele; associated with lower CYP1A1 expression, increased susceptibility to pneumonia, and acute respiratory distress syndrome [R, R, R, R, R]

About 40% of people carry the ‘A’ allele, and 14% have the full ‘AA’ genotype. The ‘A’ allele is significantly more common in Europeans, where about 89% of the people carry the ‘A’ allele, and 43% have the ‘AA’ genotype.

Recommendations

Diet

Dietary Zinc

Zinc deficiency has been found to decrease the expression of CYP1A1 in cells [R].

In a study of 116 people, those who developed ARDS had lower blood zinc levels than both people in the ICU who didn’t develop this complication and healthy volunteers. The same study found that zinc deficiency stimulated the development of lung injuries due to mechanical ventilation in mice [R].

The richest sources of dietary zinc include beef, pork, and seafood [R].

Cruciferous Vegetables

We don’t know for sure if cruciferous veggies increase CYP1A1 expression in humans. However, several studies have found that indole-3-carbinol, a substance found in cruciferous vegetables, increased CYP1A1 levels in human cells and rats [R, R, R].

Garlic

Garlic oil was shown to increase CYP1A1 levels in rats [R]. There are no studies in humans that look at the levels of CYP1A1 directly, but one study in humans does show that garlic increases Ahr, an activator of CYP1A1 [R].

Studies in humans suggest that garlic may help reduce the severity and duration of respiratory infections. It increased the number of immune cells (T cells and NK cells), boosting the immune system while lowering inflammatory proteins (cytokines) [R, R, R].

Supplements

Omega-3 Fatty Acids

Fish oil increased CYP1A1 in rats [R]. However, it’s still a question if it has the same effect in humans.

2 meta-analyses concluded that omega-3 supplementation is beneficial to improve ARDS symptoms and reduce its death rate [R, R].

Andrographis

Two studies found that andrographis increased CYP1A1 in mouse cells [R, R]. However, this effect of andrographis has not yet been confirmed in humans.

A meta-analysis of 33 trials with over 7k people suggests that andrographis can help reduce the severity and duration of respiratory infections [R]. There are also promising studies looking into the effects of andrographis in people with pneumonia [R].

Quercetin

Quercetin is a dietary polyphenol found in plant foods, including red grapes, onions, green tea, apples, berries, and Ginkgo biloba.

Studies in cells suggest that quercetin increases CYP1A1 activity [R, R, R].

In a clinical trial on 102 male smokers, both eating an antioxidant diet (including berries, green vegetables, nuts, green tea, dark chocolate, and olive oil) and eating 3 kiwifruits/day (which are a rich source of polyphenols including quercetin) increased the expression of AhR, and activator of CYP1A1 [R].

Importantly, quercetin decreased total sick days and severity of respiratory infections in middle aged and older subjects, but only in those who rated themselves as physically fit [R].

Quercetin also prevented the worsening of lung disease in mice with lung issues (COPD) infected by a rhinovirus [R].

Cruciferous vegetables, garlic, omega-3 (fish oil), andrographis, and quercetin were shown to increase CYP1A1 in animal studies and human cells.

Biljana Novkovic

PhD

Biljana received her PhD in Ecological Genetics from Hokkaido University.

Before joining SelfHacked, she was a research scientist with extensive field and laboratory experience. She spent 4 years reviewing the scientific literature on supplements, lab tests and other areas of health sciences. She is passionate about releasing the most accurate science & health information available on topics, and she's meticulous when writing and reviewing articles to make sure the science is sound. She believes that SelfHacked has the best science that is also layperson-friendly on the web.

Disclaimer

The information on this website has not been evaluated by the Food & Drug Administration or any other official medical body. This information is presented for educational purposes only, and may not be used to diagnose or treat any illness or disease.

Also keep in mind that the “Risk Score” presented in this post is based only on a select number of SNPs, and therefore only represents a small portion of your total risk as an individual. Furthermore, these analyses are based primarily on associational studies, which do not necessarily imply causation. Finally, many other (non-genetic) factors can also play a significant role in the development of a disease or health condition — therefore, carrying any of the risk-associated genotypes discussed in this post does not necessarily mean you are at increased risk of developing a major health condition.

Always consult your doctor before acting on any information or recommendations discussed in this post — especially if you are pregnant, nursing, taking medication, or have been officially diagnosed with a medical condition.

More respiratory health blogs

Can This Gene Protect You From Lung Failure? (IL17A) Can This Inflammation Gene Affect Susceptibility To Lung Failure? (TNF) The Genetic Link Between Inflammation and Lung Failure (IL8) Can This Gene Increase the Risk of Pneumonia and ARDS? (CYP1A1) Can This Master-Switch Gene Protect Against ARDS? (AHR) Can This Gene Protect You From Lung Failure? (IL13) What Role Does This Immunoglobulin Play in Lung Failure? (AGER) Does This Cannabinoid Gene Increase The Risk Of ARDS? (FAAH) Genetic Factor for Lung Failure and Inflammation (MYD88) The Role of Genes in Lung Failure Severity (MAP3K1)

Content

What is CYP1A1? CYP1A1, Pneumonia, and ARDS Potential Mechanisms Your CYP1A1 Results for Pneumonia / ARDS

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