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SMAD3

Can Allergies Cause Permanent Tissue Changes? (SMAD3)

Written by Jasmine Foster, BSc, BEd on October 22nd, 2020

The TGFb/SMAD3 pathway has both pro- and anti-inflammatory effects. Could SMAD3 variants lead to permanent tissue damage in people with allergies? Find out here.

Summary

SMAD3 encodes mothers against decapentaplegic homolog 3. Variants of SMAD3 may play a role in allergies by enhancing the inflammatory effects of TGF-beta. Lifestyle, diet, and supplement modifications may counteract the effects of these variants by preventing TGF-beta-induced tissue damage.

SMAD3 and Allergies

The SMAD3 gene encodes a protein called mothers against decapentaplegic homolog 3. This protein transmits signals from the surface of cells into the nucleus, where the DNA is stored [R, R].

SMAD3 is activated by TGF-beta, a cytokine that affects the growth, proliferation, and repair of many cell types. TGF-beta is essential for survival, and it can have both pro- and anti-inflammatory effects [R].

In asthma, TGF-beta is assumed to promote allergen tolerance [R].

Ongoing studies are looking to see if TGF-beta in the gut area can help create oral tolerance in people with food allergies. TGF-beta may promote the formation of Tregs, a type of immune cell that prevents inflammatory reactions [R].

Some research suggests that the anti-inflammatory functions of TGF-beta are accomplished through SMAD3 activation. In the absence of SMAD3, TGF-beta cannot block the production of inflammatory cytokines; in this way, low SMAD3 may make cells and tissues more susceptible to hypersensitivity reactions [R, R].

On the other hand, high TGF-beta levels have been linked to irreversible tissue changes in the airways and in other systems. SMAD3 may be the key to triggering the anti-inflammatory effects of TGF-beta and reducing the risk of permanent damage [R, R].

SMAD3 is activated by TGF-beta and may regulate this cytokine’s anti-inflammatory effects. In the absence of SMAD3, TGF-beta has no anti-inflammatory effect and can cause permanent tissue damage.

Your SMAD3 Results for Allergies

SNP Table

variant	genotype	frequency	risk allele
rs17228058
rs72743461
rs56062135
rs17294280
rs17293632

SMAD3 rs17228058

‘A’ = Not associated with allergic disorders
‘G’ = Associated with allergic disorders
The ‘G’ allele may reduce SMAD3 activity, thereby blocking the anti-inflammatory action of TGF-beta [R].

SMAD3 rs72743461

‘C’ = Not associated with allergic disorders
‘A’ = Associated with allergic disorders
The ‘A’ allele may reduce SMAD3 activity, thereby blocking the anti-inflammatory action of TGF-beta [R].

SMAD3 rs56062135

‘C’ = Not associated with allergic disorders
‘T’ = Associated with allergic disorders
The ‘T’ allele may reduce SMAD3 activity, thereby blocking the anti-inflammatory action of TGF-beta [R].

SMAD3 rs17294280

‘A’ = Not associated with allergic disorders
‘G’ = Associated with allergic disorders
The ‘G’ allele may reduce SMAD3 activity, thereby blocking the anti-inflammatory action of TGF-beta [R].

SMAD3 rs17293632

‘C’ = Not associated with allergic disorders
‘T’ = Associated with allergic disorders
The ‘T’ allele may reduce SMAD3 activity, thereby blocking the anti-inflammatory action of TGF-beta [R].

Recommendations

Avoid Air Pollution

TGF-beta without SMAD3 fails to block inflammation and may lead to irreversible tissue changes. Air pollution may cause lung damage by triggering an increase in TGF-beta; this could be especially dangerous for people with detrimental SMAD3 variants [R, R].

Research has associated exposure to air pollution with higher odds of allergic conditions, especially asthma and allergic rhinitis [R, R, R].

Try spending more time in nature and non-industrialized environments to prevent and relieve allergies.

Air pollution increases TGF-beta, which may cause irreversible tissue damage, especially in people whose SMAD3 gene fails to produce anti-inflammatory signals.

Vitamin E

In mice, increased vitamin E intake prevented tissue damage from elevated TGF-beta [R].

Several studies have associated high intake of vitamin E with a reduced incidence of asthma, while a diet poor in this vitamin increases the risk. Similarly, some people with asthma have lower levels of this vitamin in the blood and lungs [R, R, R, R, R].

Food sources of vitamin E include wheat germ, nuts, sunflower and sesame seeds, and their respective plant oils [R].

Increased vitamin E intake may help prevent the tissue damage caused by high TGF-beta.

Caffeine

In cell studies, caffeine strongly inhibits the detrimental tissue changes triggered by TGF-beta [R].

According to a review of 7 clinical studies, caffeine can help open the airways and relieve bronchitis symptoms including wheezing, coughing, and breathlessness. The effect is similar to that of the anti-asthmatic drug theophylline. Theophylline and caffeine are very similar in structure but caffeine’s effects are shorter-lived (they last only up to 4 hours) [R, R].

Caffeine blocks the tissue changes caused by TGF-beta. It also opens up the airways and improves breathing for a short period of time.

Jasmine Foster

BSc, BEd

Jasmine received her BS from McGill University and her BEd from Vancouver Island University.

Jasmine loves helping people understand their brains and bodies, a passion that grew out of her dual background in biology and education. From the chem lab to the classroom, everyone has the right to learn and make informed decisions about their health.

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.

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Can Allergies Cause Permanent Tissue Changes? (SMAD3)

Summary

SMAD3 and Allergies

Your SMAD3 Results for Allergies

SNP Table

Recommendations

Avoid Air Pollution

Vitamin E

Caffeine

Disclaimer

More inflammation & autoimmunity blogs

More allergies blogs

Content

Unlock Personalized Results And So Much More!

Essential Bundle

Essential

Bundle

Limited time offer 25% off

Ultimate Bundle

Policies

About

Navigation

Health reports