C-Reactive Protein Gene: Marker of Inflammation

Chronic inflammation is the driver of many common diseases such as heart attacks, diabetes, obesity, and autoimmune diseases. Measuring C-reactive protein (CRP) through a simple blood test is one way to know if you have a problem with chronic inflammation. It is an easy biomarker to test, and it gives you a way to quantify your inflammation level.

Some people have variants in the CRP gene that naturally elevate their CRP levels a little bit — others carry genetic variants that decrease their CRP levels. This can be important to know if you are tracking CRP as a health biomarker! Up to half of the variation seen in CRP levels is due to genetics.[ref]

What is C-reactive Protein?

Your liver produces C-reactive protein in response to both acute and chronic inflammatory conditions that cause a rise in IL-6.

Macrophages, an important part of your body’s immune response, produce IL-6 in response to specific pathogens. The “C” in C-reactive protein comes from the initial discovery that it was produced in response to the C polysaccharide found on the cell wall of pneumococcus bacteria.

Elevated CRP levels:

Really high CRP levels can indicate an acute bacterial infection or injury/wound. CRP levels can rise 2,000-fold in hours as an acute response to a pathogen. The CRP binds to a molecule on bacteria or dead cells, marking them to be cleared away by the immune system. This is an important way your body fights off invaders.

Chronically elevated CRP levels, though, are not a good thing. They are indicative of chronic inflammation, which is linked to increased risk of heart disease, depression, diabetes, obesity, and non-alcoholic fatty liver disease[ref][ref][ref][ref][ref].

Normal CRP levels:

Normal C-reactive protein levels are between 1.0 and 3.0.  Higher than 3.0 is considered ‘high’ and is used by doctors to determine heart health risk.


CRP Gene Variants:

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Genetic variants that lower CRP are linked to a decreased risk of chronic diseases; variants that cause higher CRP are linked to increased risk of chronic diseases including cardiovascular disease.[ref]

To some extent, the link between the genetic variants and disease help to answer the question of whether CRP is just a ‘marker of inflammation’ or playing a role in causing the disease. In heart disease, CRP may be actively causing atherosclerosis (hardening of the arteries)[ref], thus the increased risk of heart disease. It is also theorized that higher CRP levels may also affect fat cells and increase weight.[ref]

Check your genetic data for rs1205 (23andMe v4, v5, AncestryDNA):

  • C/C: typical
  • C/T: lower CRP, decreased risk of heart disease, colon cancer
  • T/T: lower CRP[ref][ref] decreased risk of heart disease [ref] decreased risk of lupus[ref] decreased risk of colon cancer[ref]

Members: Your genotype for rs1205 is .

Check your genetic data for rs3093058 (23andMe v4, AncestryDNA)*:

  • A/A: increased CRP [ref]
  • A/T: increased CRP
  • T/T: typical

Members: Your genotype for rs3093058 is .

Check your genetic data for rs1800947 (23andMe v4, AncestryDNA)*:

  • G/G: lower CRP,[ref] less of an increase in CRP after surgery.[ref] decreased risk of heart disease[ref], a decreased risk of diabetes[ref] increased risk of colon cancer [ref]
  • C/G: lower CRP, less increase in CRP after surgery, decreased the risk of heart disease, diabetes
  • C/C: typical CRP

Members: Your genotype for rs1800947 is .

Check your genetic data for rs3093059 (23andMe v4, v5, AncestryDNA):

  • G/G: increased CRP[ref], increased risk of type 2 diabetes[ref] [ref]
  • A/G: increase in CRP
  • A/A: typical CRP

Members: Your genotype for rs3093059 is .

Check your genetic data for rs3091244 (AncestryDNA):

  • G/G: decreased CRP [ref],
  • A/G: typical CRP
  • A/A: typical CRP, a decreased risk of lupus[ref]

Members: Your genotype for rs3091244 is .

*all risk alleles are given here in the plus orientation, but studies may refer to the risk allele on the opposite strand. 


Lifehacks:

In general, lower CRP levels should indicate lower levels of chronic inflammation. You can get your doctor to order a CRP blood test for you, or you can order it yourself through an online lab company.

Suggestions to decrease CRP levels:

The following suggestions are based on studies showing decreases in CRP levels.

Cut out trans fats:
A study of 730 nurses found that those who ate higher levels of trans fats had 73% higher CRP levels.[ref] This is an easy change to make, and trans-fats have a variety of negative health effects.

Exercise the right amount:
In patients with coronary artery disease and high CRP, exercise helped to lower CRP levels.[ref] For instance, a meta-analysis of 83 studies showed an overall positive effect of exercise for slightly lowering CRP.[ref]

On the other hand, intense exercise may increase inflammatory levels of IL-6 and CRP. [ref][ref]

Fix Sleep Apnea:
In people with sleep apnea, a CPAP machine lowered CRP and Il-6 levels.

Depression: 
People with depression are likely to have higher CRP levels. However, it isn’t clear whether the high CRP levels are causing depression or if depression is somehow causing inflammation. [ref]

Vitamin D from sun exposure?
High CRP levels are associated with low vitamin D levels.[ref] Some studies recommend raising vitamin D levels as a way of decreasing inflammation and CRP levels.  A meta-analysis of studies on vitamin D supplementation does show that it decreases CRP.[ref] So get out in the sunshine when possible, and get a vitamin D test done to see if you are low.

Sleep is important:
Sleep deprivation causes an increase in CRP levels.[ref]  Circadian misalignment also significantly increases CRP. [ref] A study of teenagers found higher CRP levels correlating to decreased sleep duration.[ref]  Thus it should be unsurprising that getting a normal amount of sleep is associated with lower CRP levels.[ref]

Vitamins and supplements only if deficient:
Adding in a supplement is a quick fix for a lot of health topics, but it seems that for lowering CRP levels, vitamins may only be effective in certain circumstances.

  • A study looking at 10 weeks of taking a mix of anti-inflammatory supplements (quercetin, EGC/G, fish oil, vitamin C, niacinamide, and folic acid) found that it did not change CRP levels.[ref]
  • Vitamin A, E, and C levels in older adults don’t affect CRP levels.[ref]
  • Magnesium supplements decrease CRP only in people with levels over 3mg/L.[ref]
  • A folate supplement (1mg/day), though, decreased CRP in obese women with PCOS.[ref]
  • People under age 60 with high baseline CRP levels may benefit a little from more vitamin C.[ref]
  • People with kidney problems and high CRP may benefit from zinc.[ref]

Diet?
With the link between higher BMI and higher CRP, it seems that diet should play a big role in CRP levels. That doesn’t seem to be the case — at least as far as popular weight loss diet trends such as low-carb or low-fat.[ref][ref]

  • Males with a high CRP and high BMI showed a small decrease in CRP when switching to a vegan diet, probably due to an increase in vegetables.[ref]
  • Sugar is often touted as inflammatory, but a meta-analysis that looked at sugar, fructose, high-fructose corn syrup, and glucose didn’t find significant interactions with CRP. [ref]
  • Neither a low-carb or low-fat diet changed CRP levels in a diet study for patients with type 2 diabetes.[ref] Nor did a low-fat, high carb diet affect CRP levels.[ref]
  • However, one dietary change that does affect CRP:  A ‘Mediterranean Diet’ has been shown to lower CRP levels.[ref] This may be due to a decrease in CRP due to higher olive oil consumption.[ref] High garlic intake is also associated with lower CRP levels.[ref]

Aspirin:
Regular aspirin use is associated with lower CRP levels.[ref] In fact, a study in patients with metabolic syndrome found that 300 mg/day of aspirin lowered CRP more than 100 mg/day of aspirin.[ref]

Moderate Wine Consumption:
Drinking moderate amounts of red wine has been shown to decrease CRP after a high-fat meal. [ref] Another study showed that red wine (but not gin!) decreased CRP levels by 21%.[ref]

Summing this all up:

Higher CRP levels increase the risk of heart disease and other chronic diseases. Your genetic variants may be playing a role in your CRP levels. The best dietary advice includes olive oil, garlic, and a Mediterranean style diet with fresh veggies — along with red wine. Sleeping is important, and so is moderate exercise in the sunshine. Sounds like a trip to the Greek isles is just what the doctor should order!


Related Genes and Topics:

Lipoprotein (a)
High Lp(a) levels are a big risk factor for sudden heart attacks. Your Lp(a) levels are mainly controlled by your genetic variants. Check to see if you carry genetic variants that increase or decrease Lp(a).

TNF-Alpha: Inflammation and Your Genes
Do you feel like you are always dealing with inflammation? Joint pain, food sensitivity, etc? Perhaps you are genetically geared towards a higher inflammatory response. Tumor necrosis factor (TNF) is an inflammatory cytokine that acts as a signaling molecule in our immune system.



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.