Genetic variants that increase susceptibility to Lyme disease

Lyme disease is transmitted by tick bites, which carry either the bacteria Borrelia burgdorferi in North America or other Borrelia species in Europe.

General symptoms of Lyme disease include a bulls-eye rash, fever, headache, pain, and general malaise. The majority of people recover after a few weeks, but some people 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 Against Borrelia:

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.

The different genetic variations in our innate immune system contribute to our individuality. 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.

Genetic Variants Linked to Lyme:

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TLR1 (Toll-like Receptor 1):
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 genetic data for rs5743618 (23andMe v4)

  • 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

Members: Your genotype for rs5743618 is .

Check your genetic data for rs5743708 (AncestryDNA)

  • A/A: less than half the risk of Lyme[ref]
  • A/G: less than half the risk of Lyme
  • G/G: typical Lyme risk

Members: Your genotype for rs5743708 is .


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, links to a greater susceptibility to antibiotic-resistant Lyme arthritis and 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? (Learn more about rheumatoid arthritis.)There have been quite a few different studies over the past 20 years looking at the link between Borrelia infection and subsequent autoimmune diseases.

Currently, there isn’t a definitive study concluding Borrelia causes autoimmune diseases (that I could find), but an interesting 2017 study looked at Lyme arthritis patients who developed autoimmune joint diseases within four 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 genetic data for rs660895 (23andMe v4, v5; AncestryDNA):

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

Members: Your genotype for rs660895 is .


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.

Herbal remedy recommendations for chronic Lyme symptoms persisting after antibiotic treatment:

Stevia, an herbal sweetener, killed Borrelia, as well as antibiotics, in the lab.[ref] I question whether this holds true in people rather than just in Petri dishes. On the other hand, stevia is probably a safe choice when you have Lyme disease, and it may be helpful.

Andrographis paniculata is an Asian herb used in traditional medicine for respiratory infections and other ailments. For chronic Lyme disease, it is recommended as an herbal remedy (combined with other herbs). 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), a traditional Peruvian herbal medicine, 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 show that it is an antiviral and immunomodulator and 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), a traditional Chinese herbal medicine, sometimes is 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 seems 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).  I guess that emodin may be the most effective constituent of some of the herbal remedies.  Rhubarb pie with some stevia?

Related Articles and Genes:

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HLA-B27: Genetic Variant That Increases Susceptibility to Autoimmune Diseases
Our immune system does an awesome job (most of the time) of fighting off pathogenic bacteria and viruses. But to fight off these pathogens, the body needs to know that they are the bad guys. This is where the HLA system comes in.

Post Treatment Lyme Disease Syndrome
Lyme disease affects 300,000 people a year in the US, mostly in the Northeast and upper Midwest but found in almost all states. It is also a disease that is controversial, causing heated online arguments, misunderstood patients, and sometimes wacky cures.