Genetic variants that increase susceptibility to Lyme disease

Lyme disease is caused by being bitten by a tick that carries the bacterium Borrelia burgdorferi in North America or other Borrelia species in Europe.  General symptoms after being bitten can include a bulls-eye rash, fever, headache, pain, and general malaise. The majority of people recover after a few weeks, but some have symptoms (neurological, cardiovascular, fatigue, arthritis) that can last for months or even years.

Whether you are one of the ones who recover quickly or have chronic symptoms including joint pain or arthritis may be due to genetic variants that you carry.

Immune Response:
The innate immune system reacts quickly to pathogens, giving us the initial inflammatory response to fight off bacterial invaders.  One part of the innate immune system is the toll-like receptor (TLR) family, which helps the body to recognize specific bacteria, like Borrelia.

The simplified picture is that the innate immune system recognizes the Borrelia bacteria, raises an alarm bringing in inflammatory molecules to destroy it. It is the front line of the body’s army, quick to rise and fight a short battle.

Part of our individuality is found in different genetic variants in our innate immune system. It makes sense for a population to carry different variants – some may be better at fighting off leprosy, others good at surviving cholera.  While variation is good on whole, for an individual, though, it can end up causing increased susceptibility to a pathogen like Borrelia.

TLR1 (Toll-like Receptor 1) -Check your Genetic Variants:

One variant in TLR1, rs5743618 or T1805G, causes a decreased TLR1 functionality for people carrying the C/C genotype.  This is an advantage when it comes to leprosy and cuts the risk of severity. [ref] But when it comes to Lyme disease, this variant is linked to an increased risk of ‘antibiotic refractory Lyme arthritis’ which basically means that joints still ache after taking several rounds of antibiotics.[ref]

The C variant for rs5743618 is found in about 50% of the Caucasian population, less than 10% of African populations, and is rarely found in Asian populations.[ref]

Check your 23andMe results for rs5743618 (v4, v5)

  • C/C: 1.9x more likely to have antibiotic-refractory Lyme arthritis (but better off if you get leprosy)
  • A/C: typical Lyme risk
  • A/A: typical Lyme risk

There is another (uncommon) TLR2 genetic variant that is not covered by 23andMe testing. It is interesting because it cuts a person’s risk of Lyme disease by more than half and reduces the risk of long-term effects from Lyme even more substantially.[ref] This again shows the impact that our genetic variants in our immune system can have on our susceptibility to diseases.

HLA-DRB1 gene:

The HLA genes code for another part of our innate immune system known as the major histocompatibility complex. One variant, HLA-DRB1 *0401 has been linked to a greater susceptibility to antibiotic-resistant Lyme arthritis as well as being a risk factor for rheumatoid arthritis.[ref][ref][ref][ref]

So why am I going on about the link to rheumatoid arthritis, an autoimmune condition? There have been quite a few different studies over the past 20 years looking at the link between Borrelia infection and subsequent autoimmune diseases. There doesn’t seem to be a smoking gun study that definitively shows Borrelia causing autoimmune diseases (that I could find), but an interesting 2017 study looked at patients with Lyme arthritis who were diagnosed with autoimmune joint diseases within 4 months of getting Lyme.  The study results showed: “Most systemic autoimmune patients had positive tests for B. burgdorferi IgG antibodies by ELISA, but they had significantly lower titers and lower frequencies of Lyme-associated autoantibodies than LA patients. Prior to our evaluation, the patients often received additional antibiotics for presumed Lyme arthritis without benefit. We prescribed anti-inflammatory therapies, most commonly disease-modifying anti-rheumatic drugs (DMARDs), resulting in improvement.”[ref]

HLA-DRB1 *0401

Check your 23andMe results for rs660895 (v4, v5):

  • G/G: increased risk of Lyme arthritis, rheumatoid arthritis.
  • A/G: increased risk of rheumatoid arthritis
  • A/A: typical risk


Other factors affecting Lyme:

A study found that age is a factor in susceptibility to Lyme with elderly people likely to have a less vigorous immune response to the pathogen. The study also found that BMI, gender, vitamin D levels, and previous exposure to Borrelia had no effect on Lyme susceptibility.[ref]


Antibiotics are, of course, the first line of defense against Borrelia. Your doctor can give you more information on effective antibiotics.

Below are some herbal remedies that are often recommended for chronic Lyme symptoms that persist after antibiotic treatment:

Stevia, an herbal sweetener, has been shown in the lab to kill Borrelia as well as antibiotics do.[ref] I question whether this holds true in people rather than just in Petri dishes. But if you like stevia, it is probably a safe bet to use it when you have Lyme disease and it may help.

Andrographis paniculata is an Asian herb used in traditional medicine for respiratory infections and other ailments. It is recommended as an herbal remedy (combined with other herbs) for chronic Lyme disease.  While I didn’t find any studies on its effectiveness against Borrelia, there are quite a few studies on it for other diseases.  Studies have found it to be somewhat effective in the treatment of ulcerative colitis,  changing TH1/TH17 immune response, decreasing fatigue from MS, and as an antibiotic. [ref][ref][ref][ref]

Cat’s Claw (Uncaria tomentosa) is a traditional Peruvian herbal medicine that is often suggested for Lyme disease.  Again, I didn’t find any studies specifically showing that Cat’s Claw was effective for chronic Lyme disease symptoms. Studies do show that it is an antiviral and immunomodulator and that it may be effective for Dengue fever. Other studies show it affecting TNF-alpha and IL-1B levels in the immune response.[ref][ref][ref] You can get Cat’s Claw online or at most health food stores.

Japanese Knotweed (Polygonum multiflorum) is a traditional Chinese herbal medicine sometimes recommended for Lyme. No Lyme specific studies, but there is a very good review of the effectiveness and safety of knotweed for a variety of ailments. Two constituents of knotweed are resveratrol and emodin.[ref]

Emodin, found in knotweed (above), is an anthraquinone that has been shown in a cell study to be effective against Borrelia.[ref] It is also found in rhubarb and is what causes the ‘gastrointestinal effects’ from eating too much rhubarb at once. Another source for emodin is cascara sagrada (also a laxative). There are quite a few studies on emodin, and it is possibly effective as an antimicrobial and as an anticancer agent. Studies also show that long-term, high doses may not be completely safe — so read up on it and know what you are getting into before you go overboard on this one.[ref] [ref]

All in all, there isn’t a ton of research on herbal remedies for chronic Lyme disease, even though there is a lot of discussion on various websites touting their effectiveness (and sometimes selling the products).  My guess is that emodin may be the most effective constituent of some of the herbal remedies.  Rhubarb pie with some stevia?

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 from Colorado School of Mines. 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.