Chronic Inflammation & Autoimmune Risk: IL17 gene variants

Inflammation can be blamed for everything from heart disease to mood disorders to obesity. Yet, how does this somewhat nebulous idea of too much inflammation tie into our genes? It seems that some people have a more sensitive immune system and are more prone to inflammatory reactions.

Inflammation and IL-17:

Interleukin-17 (IL-17A gene) is a pro-inflammatory cytokine produced by T-helper cells. It is part of our immune system — necessary in times of injury or pathogenic infection but problematic if overactive.[ref]

A quick overview of the immune system:

Our immune system’s composition includes many different parts and is responsible both for fighting off foreign pathogens (bacteria, viruses, etc.) and clearing out old or defective cells in the body. Thus, the immune system needs to recognize which cells are pathogens and which cells are part of the body. T-cells, also called T-lymphocytes, are a type of white blood cell that seeks out and destroys pathogens. There are two types of T-cells, T-helper cells and T-effector cells. T helper cells help to organize the immune response against a pathogen.

Going a little deeper here… multiple types of T-helper cells secrete different cytokines needed for different types of immune responses. One of the T-helper cells is Th17, which secretes the inflammatory cytokine IL-17 (interleukin-17).[ref]

IL-17 in Inflammation and Autoimmunity:

IL-17, produced by Th17, is important in eliminating bacteria and fungi both inside cells and outside cells.[ref]

IL-17 has six different subtypes, from IL-17A to IL-17F. As inflammatory signaling molecules, both IL17A and F act on the same receptor (IL-17R).

The IL-17 receptor is found in a variety of different cell types, and by activating the receptor, a number of different pro-inflammatory responses can happen. For example, in fungal infections, IL17 signaling can directly increase ROS production to fight off the fungus.[ref]

One of the main roles of IL17 is to protect ‘barrier integrity’ – the body’s front line against outside invaders. This means that the IL-17 receptor is found in skin tissue, mucosal tissue, the lungs, and other epithelial cells, such as those lining the intestines. One role of IL-17 is to maintain the tight junctions between the epithelial cells, and another action is to induce the release of antimicrobial chemokines in response to pathogens.[ref]

Increased risk for autoimmune diseases:

The flip side of this awesome fighter of pathogens is that IL-17 can cause damage to your tissues if it is too active. Research shows that IL-17 genetic variants can be a causative factor in several different autoimmune diseases.[ref][ref]

IL-17 is implicated in increasing the risk for several autoimmune diseases, including psoriasis, Hashimoto’s, and asthma. As mentioned above, IL-17 is mainly active in the epithelial and mucosal regions (lungs, gastrointestinal tract, skin), which explains its role in psoriasis, asthma, and other related conditions.

Genetic variants that increase the body’s production of IL-17A are a risk factor for inflammatory bowel disease (IBD), psoriasis, rheumatoid arthritis, bronchitis severity, gastric cancer, and more.

IL-17A is also implicated in celiac disease, with increased expression of IL-17A found in the intestinal mucosa of Celiac patients. Gluten sensitivity, though, was not found to increase IL-17A.[ref][ref]

IL-17 Genotype Report

There are genetic variations in IL-17 causing it to be either more active than normal (increasing risk of autoimmune/inflammatory conditions) – OR – less active than normal (protective against autoimmune/inflammatory conditions).

As is almost always the case, diet and environment interact with genetics in the development of chronic diseases. Thus, just carrying the variant doesn’t cause inflammatory diseases, per se, but instead increases the susceptibility to them in conjunction with other factors.

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Variants that cause IL-17A to be more active:

Studies show the rs2275913 variant (A/A and A/G genotypes) increases the risk of autoimmune diseases, periodontal disease, gastric cancer, and inflammatory bowel diseases. There are hundreds of studies on this variant in different population groups, confirming the increase in IL-17A and an increased risk of inflammatory conditions.

Check your genetic data for rs2275913 G197A (23andMe v4, v5; AncestryDNA )

  • A/A: Increased risk of: inflammatory diseases including periodontal, inflammatory bowel disease[ref][ref]; asthma[ref][ref]; digestive system neoplasms[ref] rheumatoid arthritis[ref]; periodontitis[ref] 3-fold increased risk of COPD (smokers)[ref]. Protective against: Brucella species (brucellosis, bacterial infection)[ref], tuberculosis[ref], hepatitis-B[ref]
  • A/G: somewhat increased risk of the above inflammatory conditions
  • G/G: typical risk

Members: Your genotype for rs2275913 is .

Protecting against infectious disease: The rs2275913 A/A genotype is protective against infection with Brucella species (brucellosis, bacterial infection)[ref], and against tuberculosis[ref]. Other studies note that people with the AA variant were less likely to get tuberculosis, but if they did get it, the disease’s symptoms could be more severe.[ref] A study in a Chinese population group found that those with A/A or A/G were less likely to get hepatitis-B.[ref]

Check your genetic data for rs279548 (23andMe v5 only):

  • T/T: somewhat increased IL17A, increased risk of asthma[ref]
  • C/T: a minor increase in the risk of asthma
  • C/C: typical

Members: Your genotype for rs279548 is .

Variants that cause IL-17A to be less active:

These variants are linked to a decreased risk of autoimmune diseases in some populations, indicating that IL-17 may be somewhat less active.

Check your genetic data for rs8193037 (23andMe v4; AncestryDNA)

  • A/A: possibly protective against inflammatory conditions, decreased IL-17A[ref][ref]
  • A/G: possibly protective against inflammatory conditions, decreased IL-17A
  • G/G: typical

Members: Your genotype for rs8193037 is .

Check your genetic data for rs3819025 (23andMe v4)

  • A/A: possibly protective against inflammatory conditions, including autoimmune thyroid[ref]
  • A/G: possibly protective against inflammatory conditions
  • G/G: typical

Members: Your genotype for rs3819025 is .

IL-17F genetic variants (more active):

IL-17F is also expressed by Th17 cells.[ref]

Check your genetic data for rs763780 G7488A (23andMe V5 only)

  • T/T: typical
  • C/T: increased risk of rheumatoid arthritis
  • C/C: increased risk of digestive system neoplasms[ref],increased risk of rheumatoid arthritis[ref][ref], increased risk of autoimmune thyroid disease[ref], increased risk of vaginal candidiasis[ref]

Members: Your genotype for rs763780 is .


Lifehacks for decreasing high IL-17

If you have an increased IL-17 response that is exacerbating an inflammatory condition, you may want to look into natural ways to decrease IL17.

Keep in mind that tamping down IL-17 may not be a good idea if you’re also trying to fight off a pathogen. Talk with your doctor if you have any questions about supplements and their interactions with medications.

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About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and also an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.

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