Are You Genetically Susceptible to Post-Treatment Lyme? (ABCB1)

Lyme disease is a debilitating illness caused by an infection of Borrelia burgdorferi bacteria, typically transmitted to humans by tick bites. In most cases, Lyme can be successfully treated with a course of antibiotics, after which the patient returns to full health. Mysteriously, however, some people suffer from fatigue, pain, and difficulty thinking (brain fog) for months or years after the infection [R, R].

This is post-treatment Lyme disease syndrome (PTLDS): a condition that extends and persists after the normal course of Lyme [R].

Researchers have long been baffled about why some people suffer post-treatment Lyme symptoms and others don’t. Recently, some have begun to suspect that our DNA plays a role.

Post-treatment Lyme disease syndrome is a condition that develops after an acute Borrelia burgdorferi infection is resolved. It causes fatigue, pain, and brain fog, and it may have a genetic component.

ABCB1, sometimes called MDR1 (for multi-drug resistance gene 1) codes for a protein called P-glycoprotein (P-gp) [R, R].

This troublesome little protein has been the subject of study because of its involvement in drug resistance; people with certain variants in ABCB1 have higher P-gp activity and require more of a given drug (like antidepressants or HIV medications) or may not respond to some treatments at all [R, R].

People with low P-gp activity may also be at risk of cancers that don’t respond to conventional chemotherapy treatment [R].

Can a Transport Protein Prevent Post-Treatment Lyme?

Like so many things, however, P-glycoprotein is a double-edged sword: higher P-gp activity increases drug resistance (which can make it difficult to treat depression, cancer, and other conditions), but it may also protect against post-treatment Lyme disease syndrome[R, R].

Here’s how researchers think it could work:

Inducing Autoimmunity

A tick bites a human host, and Borrelia burgdorferi is transmitted into the skin. It multiplies and spreads, and the immune system mounts an inflammatory defense. This inflammatory response creates the symptoms of Lyme: fever, headache, fatigue, and rash. Doctors prescribe a course of antibiotics, and the bacteria die off in a few weeks [R, R].

During the immune response, however, white blood cells are exposed to bacterial proteins, which may be similar enough to human enzymes to induce autoimmunity [R, R].

One possible target is an enzyme called enolase, which is needed to release energy from glucose during glycolysis. Humans and bacteria both have a version of enolase, and if the immune system produces antibodies against bacterial enolase, those antibodies risk attacking human enolase as well [R].

The autoimmune theory gets further support from the fact that most people who suffer from post-treatment lyme don’t have any detectable Borrelia bacteria left in their bodies after antibiotic treatment. Plus, Borrelia doesn’t produce toxins, so the illness must be coming from something else—like autoantibodies [R, R].

Flushing the Threat

P-glycoprotein’s job is to remove xenobiotics—compounds produced by bacteria and other potential pathogens—that make their way into our cells [R].

P-gp may therefore protect against post-treatment Lyme symptoms by flushing Borrelia proteins, thereby preventing your body from producing antibodies that react to both bacterial and human enzymes [R, R, R, R].

ABCB1 codes for P-glycoprotein, a transporter that flushes foreign compounds like drugs and bacterial proteins out of our cells. If P-gp isn’t working well and Borrelia enzymes remain in the cell, some people may develop autoimmune reactions.

According to a recent study, the more P-gp-reducing variations someone has in their ABCB1 gene, the more likely they are to suffer from post-treatment Lyme disease syndrome after an acute Borrelia infection [R].

The single SNP with the greatest impact is rs1128503, which has a significant effect on post-treatment Lyme predisposition on its own. The risk increases when combined with the ‘C’ allele at rs2235067; meanwhile, the rare ‘G’ allele at rs4148740 seems to improve the MDR1 transporter and decrease the risk of post-treatment Lyme [R].

Primary SNP: ABCB1 rs1128503

• ‘AG’ = Increased risk of PTLDS, decreased MDR1 protein activity
• ‘AA’ = Somewhat increased risk of PTLDS
• ‘GG’ = Normal risk of PTLDS

Other Important SNPs:

ABCB1 rs2235067

• ‘C’ = Increased risk of PTLDS, decreased MDR1 protein activity 
• ‘T’ = Decreased risk of PTLDS, increased MDR1 protein activity

ABCB1 rs4148740

• ‘A’ = Increased risk of PTLDS when combined with other risk alleles 
• ‘G’ = Decreased risk of PTLDS