gut health

FCGR2A

The Role of One Receptor in Ulcerative Colitis (FCGR2A)

Written by Aleksa Ristic, MS (Pharmacy) on May 18th, 2020

The FCGR2A gene encodes a receptor that activates the antimicrobial response. One variant in this gene is associated with ulcerative colitis—read on to learn the details and get tailored tips.

FCGR2A in Immunity and Inflammation

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The FCGR2A gene encodes a specific type of Fc receptor: FcγRIIA or CD32. Immune cells such as monocytes and macrophages express Fc receptors, which recognize antibodies attached to pathogens or infected cells [R].

Fcγ(gamma) receptors recognize IgG antibodies. While they all bind IgG1 and IgG3 antibodies, only FcγRIIA can effectively bind IgG2. Once activated, this receptor sets off different mechanisms that promote inflammation and pathogen removal [R, R, R].

Over-active CD32 can contribute to autoimmunity, while its suppression leads to poor antimicrobial response [R].

FCGR2A encodes a receptor that binds IgG antibodies and signals the immune response against pathogens. An over-active receptor can contribute to inflammation and autoimmunity.

The Role in Ulcerative Colitis

Ulcerative colitis (UC) and Crohn’s disease (CD) are the most frequent subtypes of inflammatory bowel disease (IBD). The cause of IBD lies in a complex interplay of genetic and environmental factors [R].

Ulcerative colitis typically affects the colon and rectum, and involves inflammation of the surface (mucosal) layer [R, R].

Although IBD is considered a T cell-mediated condition, recent evidence implies a dysfunction in B cells and FcγR signaling in IBD development. In patients with IBD, and especially ulcerative colitis, IgG antibodies can flag healthy gut components and trigger an autoimmune reaction [R, R, R].

Ulcerative colitis is a form of autoimmune colon inflammation. Self-destructive IgG antibodies can play a role in this condition via impaired FcγR signaling.

FCGR2A Variant and Ulcerative Colitis Susceptibility

Robust evidence suggests a link between one FCGR2A variant and ulcerative colitis. In a meta-analysis of six trials and over 26,000 participants, the “A” allele at rs1801274 was associated with 21% higher UC rates. All subjects were of European ancestry [R].

A study of over 41,000 European subjects confirmed the association between this variant and IBD. However, some studies haven’t found a significant link with Crohn’s disease, suggesting its primary role in ulcerative colitis [R, R].

The same SNP is associated with ulcerative colitis in Korean and Japanese populations, too [R, R].

The “A” allele at rs1801274 is associated with higher rates of ulcerative colitis across different populations.

IBD Complications and Dietary Factors

A meta-analysis that included 2,287 IBD patients associated this variant with 65% higher chances of IBD-associated colorectal cancer. However, when corrected for other contributing factors, the effect became non-significant [R].

A study of over 165,000 women identified one dietary factor that greatly impacts the link between rs1801274 and ulcerative colitis. In women with the “AA” genotype, iron from animal sources was associated with higher UC rates (3-fold increase for each 1 g of added iron) [R].

On the other hand, iron from animal sources was protective in women with the “GG” genotype [R].

People with rs1801274-A may be more prone to IBD-associated colon cancer. Iron from animal sources could amplify the effects of this variant.

How It Works

The G>A switch at rs1801274 changes one amino acid in the FcγRIIA structure. The “A” allele codes for histidine, which increases the receptor affinity for IgG antibodies, especially IgG2. This change improves pathogen removal but also contributes to autoimmune conditions such as ulcerative colitis [R, R].

The activation of FcγRIIA receptors on the gut immune cells triggers IL-1b production, which in turn drives Th1 7 immunity and inflammation [R, R].

Other Conditions

This variant has a well-known role in autoimmune conditions, such as:

Lupus [R]
Graves’ disease [R]
Kawasaki disease [R]

Changes in the FcγRIIA structure and function can also affect the immune response to HIV, bacterial infections, lymphomas, and more [R, R, R].

Your FCGR2A Results for Ulcerative Colitis

SNP Table

variant	genotype	frequency	risk allele
rs1801274

SNP Summary

Primary SNP:

FCGR2A rs1801274

‘G’ = not associated with ulcerative colitis
‘A’ = associated with higher rates of ulcerative colitis and complications

Population Frequency: Around 47% of European descendants carry one copy, and 26% carry both copies of the “A” allele. This allele is even more common in East Asian populations, where 43% of people have one and 51% have both copies.

Recommendations

Lifestyle

Avoid Stress

Clinical and animal studies have shown the potential of psychological stress to raise IgG antibodies, especially IgG2. Stress can also mimic your gene variant by increasing IL-1b levels and activating Th17 cells [R, R, R, R].

Psychological stress has well-known detrimental effects on gut health and inflammation. It raises gut permeability and the levels of different inflammatory cytokines [R, R].

Many ulcerative colitis patients develop anxiety and depression associated with their debilitating digestive symptoms. In turn, stress may worsen the symptoms of UC. Because of this potential feedback loop, many doctors emphasize the importance of managing the mental health of UC patients [R, R, R, R].

Psychological stress can worsen the impact of your gene variant and play a significant role in ulcerative colitis development. Try to avoid stress and practice relaxation techniques.

Moderate Sun Exposure

Sunlight is the best natural source of vitamin D, which helps combat Th17-associated inflammation. In a trial of 1,470 older people, vitamin D deficiency was associated with higher levels of IgG2 [R, R].

Additionally, UV light may counteract your FCGR2A variant by suppressing Th17 cells [R, R].

Calcium and vitamin D deficiencies are common in ulcerative colitis patients, leading to osteoporosis and joint disorders. The lack of vitamin D is also associated with increased UC severity and duration. Moderate sun exposure will help you get enough of this crucial nutrient [R, R, R].

Moderate sun exposure may lessen the impact of your variant. It supplies vitamin D, which is crucial for ulcerative colitis patients.

Diet

IgG-Based Elimination Diet

Unlike acute allergic reactions, which are IgE-mediated, most delayed food reactions (sensitivities) are IgG-mediated. Based on this feature, doctors have developed special elimination diets, excluding foods that raise IgG levels in sensitive patients [R, R, R].

In a study of 97 ulcerative colitis patients, an IgG-based elimination diet significantly reduced the symptoms and improved the quality of life. This approach may be particularly useful for people with the discussed SNP, given its effect on IgG activity [R].

A special elimination diet can remove the foods that increase IgG levels and thus potentially improve ulcerative colitis.

Limit the Intake of Iron From Animal Sources

As mentioned, iron from animal sources can amplify the impact of rs1801274-A on ulcerative colitis [R].

Red meat is the most concentrated animal source of iron. Increased intake of red or processed meat is associated with higher ulcerative colitis relapses (re-activation) [R, R].

Consider limiting the intake of pork, lamb, and beef. You can replace them with fish, chicken, and plant sources of iron. Of course, measure your ferritin and iron levels to make sure you are still getting enough iron.

To reduce the impact of your variant, limit the intake of red meat and replace it with fish, chicken, and plant sources of iron.

Supplements

Boswellia

Boswellia resin or frankincense is a natural remedy with powerful anti-inflammatory properties. It may counteract the FcγRIIA receptors by reducing IL-1b levels and Th17 activity [R, R, R].

Boswellia extract also has antioxidant activity and protects the intestinal barrier from inflammatory damage [R].

It was effective in the treatment of 30 patients with chronic colitis with minimal side effects. In another trial, Boswellia resin improved ulcerative colitis with 80-82% remission [R, R].

Boswellia resin or frankincense is a powerful anti-inflammatory. It may counteract the FcγRIIA receptors and improve the symptoms of ulcerative colitis.

Curcumin

Curcumin is the active principle of turmeric. It can suppress Th17 cells and lower IL-1b levels [R, R, R].

Multiple clinical trials have produced promising results for curcumin in IBD, and further research is currently underway [R, R, R].

Vitamin D

As mentioned, vitamin D deficiency is associated with higher Th17 activity and IgG levels [R, R].

If you can’t get enough vitamin D from sun exposure, consider taking a supplement. In a meta-analysis of 18 trials and 908 patients, vitamin D supplementation corrected a deficiency and helped prevent IBD relapse [R].

Curcumin and vitamin D may reduce the impact of your FCGR2A variant and help with ulcerative colitis.

Aleksa Ristic

MS (Pharmacy)

Aleksa received his MS in Pharmacy from the University of Belgrade, his master thesis focusing on protein sources in plant-based diets.

Aleksa is passionate about herbal pharmacy, nutrition, and functional medicine. He found a way to merge his two biggest passions—writing and health—and use them for noble purposes. His mission is to bridge the gap between science and everyday life, helping readers improve their health and feel better.

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 gut health blogs

Could This Gene Be Linked To Gut Inflammation? (ATG16L1) Could This Gene Play A Role In Inflammatory Bowel Disease? (STAT3) How Do Your Genes Respond to Dietary Fat? (TCF7L2) Do Your Genes Favor the Mediterranean Diet? (TCF7L2) How Does this Serotonin Receptor Affect Gut Inflammation? (HTR3E) The Impact of a Serotonin Receptor on IBS-D (HTR3A) How Can Neurotrophins Affect Gut Inflammation? (BDNF) Could Your IBS Symptoms Be Caused by an Enzyme Deficiency? (SI) What is the Connection Between β-Klotho and Gut Inflammation? (KLB) Can This Gene Worsen Gut Inflammation? (NOS2)

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FCGR2A in Immunity and Inflammation FCGR2A Variant and Ulcerative Colitis Susceptibility Your FCGR2A Results for Ulcerative Colitis

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