C-Reactive Protein (CRP): 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 — 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]

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What is C-reactive Protein (CRP)?

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

Macrophages, a critical part of your body’s immune response, produce IL-6 in response to specific pathogens. So CRP rises in response to inflammation.

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.  CRP binds to certain bacteria or to dead cells as a marker that they need to be cleared out.

Elevated CRP levels:

Really high CRP levels can indicate an acute bacterial infection or injury/wound. CRP levels can rise 2,000-fold in just hours as an acute response to a pathogen. 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 an 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.

Is high CRP genetic?

Genetics plays a role in your propensity towards higher or lower baseline levels of CRP. For example, if your CRP level is on the high end of normal, it may be that genetically you tend to produce more CRP.

To some extent, the link between the genetic variants and disease helps to answer whether CRP is just a ‘marker of inflammation’ or playing a role in causing the disease.

  • Genetic variants that lower CRP are linked to a decreased risk of certain chronic diseases that are thought to be caused by chronic inflammation.
  • Variants that cause higher CRP are linked to increased risk of some chronic diseases including cardiovascular disease.[ref]

Studies showing that CRP may be ‘causal’:

  • 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]
  • For type 2 diabetes, researchers find that variants linked to an increase in CRP are also linked to an increased risk of diabetes. [ref]

But other studies show that genetically higher CRP levels may not always cause diseases associated with chronic inflammation.

  • A study looking at the link between higher CRP levels in people with depression found that the genetic variants linked to higher CRP were likely not causal in depression. Instead, the researchers concluded that “CRP may be a compensatory response to external insults that predispose to depression, and that an increase in the concentration of CRP might be adaptive.”[ref]

CRP Genotype Report

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CRP gene variants linked to increased CRP include:

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 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 .

Variants linked to generally lower CRP levels:

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 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 rs3091244 (AncestryDNA):

  • G/G: lower 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.

Decreasing CRP levels naturally:

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, so you should cut them out even if your CRP is not a problem.

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 on 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 just a marker for the inflammation that is causing the depression. [ref][ref]

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]

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Diets for lowering CRP:

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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.


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.