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IL12A

Can This Gene Worsen Celiac Disease? (IL12A)

Written by Carlos Tello, PhD on May 18th, 2020

The IL12A gene encodes a protein that is combined with others to produce the cytokines IL-12, IL-23, and IL-35. Variants of this gene can contribute to celiac disease. Read on to learn if your variants are associated with this condition.

What Is the IL12A Gene?

The IL12A gene encodes IL12-p35, required to form the pro-inflammatory cytokine IL-1 2 [R, R].

IL-12 is produced by various immune cells (dendritic cells, macrophages, and B cells) in response to infections. It plays multiple roles in the immune system, including [R]:

Favoring the development of Th1 over Th2 cells [R, R, R]
Promoting the development and activity of CD8+ T cells and natural killer cells [R, R]
Stimulating IFN-γ secretion [R]

This cytokine helps fight off infections in normal conditions, but its excessive production may cause autoimmune and inflammatory diseases such as:

Rheumatoid arthritis [R]
Multiple sclerosis [R]
Autoimmune hyperthyroidism (Grave’s disease) [R]
Sjögren’s syndrome [R]
Asthma [R]
Primary biliary cirrhosis [R]

In addition, IL12-p35 can bind to other proteins and form cytokines other than IL-12 (such as IL-23 and IL-35) [R, R, R, R].

The IL12A gene encodes a protein that can bind to others to form the cytokines IL-12, IL-23, or IL-35, all of which are involved in the immune response.

IL12A and Celiac Disease

Celiac disease is an immune disorder triggered in response to gluten, a protein found in grains such as wheat, barley, and rye. The immune cells recognize gluten as a threat and mount an aggressive inflammatory response that damages the small intestine and causes digestive issues and nutrient deficiencies due to poor absorption [R, R].

More specifically, the activation of immature CD4+ T cells by gluten causes their development into Th1 cells and the release of inflammatory cytokines such as IFN-γ and IL-21 [R, R, R, R].

Although the inflamed gut lining of celiac patients has increased IL12-p35 levels, it lacks the other protein needed to produce IL-12. This suggests that the IL-12 cytokine doesn’t play a key role in celiac disease [R, R, R].

The role of IL-23 in celiac disease is unclear: a variant at the gene that encodes its receptor (IL23R) increased susceptibility to celiac disease in Spaniards but not in Dutch [R, R].

Some scientists believe that IL12A may contribute to celiac disease mainly through the production of IL-35 [R, R].

Celiac disease is a disorder in which the immune system causes inflammation and damages the small intestine in response to gluten, a protein found in most grains. The IL12A gene is believed to contribute to celiac disease through the production of IL-35.

IL12A Variants and Celiac Disease

The most widely-studied IL12A polymorphism is rs17810546, located in a region of the gene that can be bound by certain proteins to activate its expression (an enhancer). Its rare variant ‘G’ increases the expression of this protein [R].

This variant was linked to celiac disease in 5 studies on British, Italian, Dutch, Finnish, Saharawi, Irish, and Swedish-Norwegian populations, and the association was confirmed in a meta-analysis [R, R, R, R, R, R].

This polymorphism has also been associated with Behçet’s disease and juvenile arthritis, further illustrating the role of IL12-p35 in inflammatory and immune conditions [R, R, R, R].

The rs17810546 polymorphism is strongly linked to the minor ‘C’ variant of rs9811792, which was also associated with celiac disease in the same studies.

A less widely-investigated polymorphism is rs2561288, whose major allele ‘T’ was associated with a slightly increased incidence of celiac disease in a north Indian population [R].

Several IL12A variants have been associated with celiac disease. The most widely-studied one increases the expression of the gene.

Your IL12A Results for Celiac Disease

SNP Summary and Table

Primary SNP: IL12A rs17810546

‘A’ = Normal risk of celiac disease.
‘G’ = Increased risk of celiac disease.

Other Important SNPs:

IL12A rs9811792

‘T’ = Normal risk of celiac disease.
‘C’ = Increased risk of celiac disease.

IL12A rs2561288

‘T’ = Increased risk of celiac disease.
‘C’ = Lower risk of celiac disease.

Population Frequency

The ‘G’ variant at rs17810546 is very rare and 92% of the world population doesn’t carry any copies of this allele. In European and American descendants, this variant is slightly more common (~18% of carriers).

In both rs9811792 and rs2561288, the minor variant is only slightly less frequent. The most common scenario is to carry one copy of each allele, as is the case for ~44% of the world population.

SNP Table

variant	genotype	frequency	risk allele
rs17810546
rs9811792
rs2561288

Recommendations

Diet

Gluten-free Diet

The only effective treatment for celiac disease is a strict gluten-free diet, which allows the management of the symptoms in most cases. Gluten is found in the following grains and their products [R]:

Wheat
Rye
Spelt
Barley
Triticale

Although gluten seems to have no effect on IL-12 levels, it has been shown to stimulate the production of IL-23 and IL-35 [R, R, R].

Avoidance of Lectin/Other Potential Irritants

Dietary lectins may worsen inflammation in people sensitive to them. For example, lectins contributed to autoimmunity in one study with rheumatoid arthritis patients [R, R].

Preliminary research suggests that avoiding lectins may reduce the symptoms of autoimmune conditions in sensitive individuals [R].

A lectin from buckwheat stimulated dendritic cells to produce IL-12 and other pro-inflammatory cytokines in test tubes [R].

Gut damage and inflammation in celiac disease may cause temporary lactose intolerance. Such patients may need to avoid dairy until their gut lining recovers [R].

Elimination diets such as the Lectin Avoidance Diet may help identify and remove common food irritants — such as lectins, gluten, and dairy — that may be worsening autoimmunity in sensitive individuals [R, R, R].

The most effective way to treat celiac disease is to go gluten-free. Other potential irritants such as lectins and lactose may worsen autoimmunity in some people.

Lifestyle

Moderate Sun Exposure

Moderate sun exposure is the best way to get natural UV light and vitamin D, which both help suppress inflammation. Because vitamin D inhibits the development of Th1 cells, it may be beneficial in the specific case of celiac disease [R, R, R].

Vitamin D deficiency and subsequent bone issues are common in celiac disease patients, so it’s crucial to get enough of this nutrient [R, R].

Vitamin D supplementation lowered IL-12 levels in some human studies but not in others. In a study on 57 people with lupus, vitamin D deficiency was associated with increased IL-23 levels [R, R, R, R].

People with celiac disease may have vitamin D deficiency. A moderate exposure to sunlight is a good way to produce this vitamin and may reduce some cytokines associated with IL12A.

Supplements

Probiotics

Bacterial overgrowth in the small intestine may worsen celiac disease and hinder gut recovery [R].

Probiotic (Bifidobacterium spp.) supplementation in patients with celiac disease has yielded mixed results. In one trial, it improved the symptoms but not immunological markers. In another one, it only improved lab markers of inflammation [R, R].

In 109 patients with celiac disease and IBS, a mixture of probiotic strains significantly improved IBS symptoms [R].

A few studies in mice with colitis showed that supplementation with Lactobacillus or Bifidobacterium probiotics can reduce gut inflammation by blocking the IL23/Th17 axis [R, R, R].

Preliminary research suggests that some probiotics may help people with celiac disease reduce gut inflammation and damage.

Carlos Tello

PhD

Carlos received his PhD and MS from the Universidad de Sevilla.

Carlos spent 8 years in the laboratory investigating mineral transport in plants. He then started working as a freelancer, mainly in science writing, editing, and consulting. Carlos is passionate about learning the mechanisms behind biological processes and communicating science to both academic and lay audiences. He strongly believes that scientific literacy is crucial to maintaining a healthy lifestyle and avoiding falling for scams.

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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What Is the IL12A Gene? IL12A Variants and Celiac Disease Your IL12A Results for Celiac Disease

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Can This Gene Worsen Celiac Disease? (IL12A)

What Is the IL12A Gene?

IL12A and Celiac Disease

IL12A Variants and Celiac Disease

Your IL12A Results for Celiac Disease

SNP Summary and Table

Population Frequency

SNP Table

Recommendations

Diet

Gluten-free Diet

Avoidance of Lectin/Other Potential Irritants

Lifestyle

Moderate Sun Exposure

Supplements

Probiotics

Disclaimer

More gut health blogs

Content

Unlock Personalized Results And So Much More!

Essential Bundle

Essential

Bundle

Ultimate Bundle

Limited Time Offer 25% Off

Individual DNA Reports

Methylation Pathway - MTHFR Test

Histamine Intolerance DNA Pathway Report

Gut Health, Digestion & IBS DNA Report

Autoimmune Disease Risk & Prevention DNA Report

See all reports

Policies

About

Navigation

Health reports