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Increased Inflammation and IL-17A Genetic Variants

Articles about ‘inflammation’ seem to be everywhere these days, and inflammation seems to be blamed for everything from heart disease to mood disorders to obesity. But 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.

IL17A and Inflammation

Interleukin-17 (IL-17A gene) is a pro-inflammatory part of our immune system that, while necessary in times of injury or pathogenic infection, can cause problems if it is overactive.[ref] We need a balance in the body between fighting off pathogens and not having too much of an inflammatory response.

IL-17 is implicated in increasing the risk for several autoimmune diseases including psoriasis and asthma. Genetic variants that increase the body’s production of IL-17A have been shown to be a risk factor for:

  • IBD
  • rheumatoid arthritis
  • bronchitis severity
  • gastric cancer
  • celiac
  • COPD
  • 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-17A Genetic Variants:

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There are genetic variations of IL-17A that can cause 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 the case with most genetic variants, diet and environment interact with genetic susceptibility in the development of chronic diseases. Just carrying a genetic risk factor doesn’t mean you’ll get the disease.

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

Studies show that the rs2275913 variant (A/A and A/G genotypes) increases the risk of autoimmune diseases, periodontal disease, gastric cancer, and inflammatory bowel diseases.[ref][ref][ref][ref][ref] There are quite a few studies on this variant in different populations showing the increase in IL-17A and an increased risk of inflammatory conditions. In the “pro” column for this variant is the fact that overactivity may be protective against infectious diseases like tuberculosis and influenza A (H3N2).[ref][ref]

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

  • A/A: increased risk of inflammatory conditions: autoimmune, periodontal, inflammatory bowel; decreased risk of infectious diseases such as tuberculosis
  • A/G: somewhat increased risk of inflammatory conditions.
  • G/G: typical

Members: Your genotype for rs2275913 is .

Check your genetic data for rs8193036 (23andMe v4; AncestryDNA)

  • C/C: 3-fold increased risk of COPD (smokers)[ref]
  • C/T: increased risk of COPD (smokers)
  • T/T: common allele, protective against TB (Chinese Han population)[ref]

Members: Your genotype for rs8193036 is .

Variants that cause IL-17A to be 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; AncestryDNA)

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

Members: Your genotype for rs3819025 is .

 


Lifehacks:

Healthy gut: The gut microbiome is important in balancing out your immune response, and IL17 plays a role here. If you have IL-17A variants and are dealing with autoimmune disease, focusing on a healthy gut microbiome may help. This may mean adding in more fibrous vegetables or legumes to your diet, or perhaps finding the right probiotic.  [ref]

Exercise: In a study on high blood pressure, exercise immediately decreased Th17 lymphocytes. [ref]

Talk with your doctor: There are several monoclonal antibodies that target IL-17 developed as therapies for psoriasis. [ref]

DHA and EPA: Increasing DHA and EPA (through fish oil supplements) has been shown to decrease IL-17 levels in patients with periodontitis. [ref]

Related article: specialized pro-resolving mediators from DHA/EPA and the resolution of inflammation

Sprinkle on the spices: Ursolic acid, which is a natural carboxylic acid found in rosemary and thyme, is a strong inhibitor of IL-17. [ref] It is also a component of rosemary extract, which was traditionally used for treating rashes, wounds, dyspepsia, etc.[ref]

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Related Articles and Genes:

Vitamin D, Genes, and Your Immune System
Vitamin D is more than just a ‘vitamin’. It is actually a hormone that is essential to so many processes in your body – including your immune system.

TNF-alpha: Inflammation and Your Genes
Do you feel like you are always dealing with inflammation? Joint pain, food sensitivity, skin issues, gum disease, etc… It could be that your body is genetically gearing towards a higher inflammatory response due to high TNF-alpha levels.

Originally published 1/16/17, updated 1/2022

 


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 from Colorado School of Mines and 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.