Lyme disease, also know as Lyme borreliosis, is an illness caused by the spirochete bacterium Borrelia burgdorferi. Lyme disease is generally transmitted via tick bites, and is the most common vector-borne disease in the United States. A common sign of Lyme infection is the erythema migrans lesion at the site of the bite, though this rash is absent in roughly a quarter of cases. If untreated, Lyme disease can progress through a series of phases and ultimately damage the joints, heart, and nervous system. Lyme disease is commonly treated with antibiotics, although antibiotic resistance has been reported.
Two SNPs have been identified that are associated with Lyme disease, and may be associated with the progression of the disease. Both SNPs occur in genes in the Toll-like receptor family, a class of cell surface receptors involved in the innate immune system.
A 2005 study identified rs5743708 as a potentially protective variant against the progression of Lyme disease [PMID 16081826]. This study examined 155 Lyme disease patients with matched controls and found that the rs5743708 polymorphism may influence disease progression. Rs5743708 is a SNP in the protein-coding region of the Toll-like receptor 2 (TLR2) gene on chromosome 4, and causes an arginine to glutamine amino acid substitution at position 753 of the TLR2 protein. All patients in the study were either heterozygous for the risk allele (AG) or had the normal genotype (GG); no homozygous (AA) patients were identified. The researchers found that the AG risk variant occurs significantly less frequently in Lyme disease patients compared with controls (OR = 0.393, P = 0.033). This interaction is even more pronounced among patients with advanced-stage Lyme disease (OR = 0.163, P = 0.018). The authors hypothesize that rs5743708 may protect against the progression of Lyme disease by reducing TLR2 signaling, thereby preventing activation of the immune system, which is hypothesized to exacerbate symptoms of Lyme disease.
A 2012 study implicated rs5743618 in Lyme disease progression [PMID 22246581]. Rs5743618 is a SNP at nucleotide position 1805 in the protein-coding region of Toll-like receptor 1 (TLR1) gene. The authors examined 248 Caucasian patients with Lyme disease and found that homozygous GG individuals may be more likely to develop antibiotic-resistant Lyme arthritis. The 1805GG variant was found in 51% of patients displaying a Lyme rash, while the frequency of this polymorphism was 47% in patients with antibiotic-responsive arthritis and 62% in patients with antibiotic-resistant arthritis. Patients with antibiotic-resistant Lyme arthritis had an increased frequency of the GG variant compared with patients displaying a Lyme rash only (OR = 1.7, P = 0.1) or patients with antibiotic-responsive arthritis (OR = 1.9, P = 0.05). Though these p-values are of borderline statistical significance, the authors claim that the odds ratios are typical of comparable autoimmune arthritis cases.