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 genetics in the development of chronic diseases.

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 infective diseases like tuberculosis.[ref]

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

  • A/A: increased risk of inflammatory conditions: autoimmune, periodontal, inflammatory bowel
  • 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:

Curcumin (in an animal study) was found to decrease IL-17.  The spice turmeric is high in curcumin, or you can find curcumin as a supplement.

Vitamin D (in vitro study) may decrease high IL-17 levels.  Get out in the sunshine, or look into supplementing with vitamin D (do a blood test first to determine your vitamin D status).  Be sure to read the labels on the vitamin D supplement and go for a vitamin D3 without soybean or cottonseed oil.

More to Read:

IL-17A variants don’t act alone in increasing susceptibility to inflammatory conditions; environmental elements play a role as well.

 

Originally published 1/16/17, updated 10/11/18.

 



Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University and an undergraduate degree in engineering. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between the research hidden in scientific journals and everyone's ability to use that information. To contact Debbie, visit the contact page.