Toll-like Receptor Polymorphisms Are Associated with Increased Neurosyphilis Risk

Overview

Journal Sex Transm Dis

Specialty Infectious Diseases

Date 2014 Jun 13

PMID 24922103

Citations 17

Authors

Christina M Marra

Sharon K Sahi

Lauren C Tantalo

Emily L Ho

Shelia B Dunaway

Trudy Jones

Thomas R Hawn

Affiliations

Soon will be listed here.

Abstract

Background: Single-nucleotide polymorphisms (SNPs) in toll-like receptors (TLR) 1, 2, and 6 impair cell signaling in response to spirochetal lipoproteins. We investigated whether common SNPs in TLR1, TLR2, or TLR6 were associated with laboratory- or clinically-defined neurosyphilis.

Methods: Polymorphisms in the genes for TLR1 (a T→G mutation at position 1805), TLR2 (a G→A mutation at position 2258), and TLR6 (a C→T mutation at position 745) were sought in 456 white patients with syphilis. Laboratory-defined neurosyphilis included a reactive cerebrospinal fluid (CSF)-Venereal Disease Research Laboratory (VDRL) test. Clinically-defined neurosyphilis included new vision or hearing loss. Controls had CSF white blood cells of 5/μL or less, nonreactive CSF-Venereal Disease Research Laboratory, and no vision or hearing loss.

Results: Overall, 26.2% of patients had laboratory-defined and 36.2% had clinically-defined neurosyphilis. Compared with controls, patients with any of the 3 SNPs were more likely to have laboratory-defined neurosyphilis. Those with TLR2 or TLR6 SNPs were more likely to have clinically-defined neurosyphilis. These associations were independent of serum rapid plasma reagin titer.

Conclusions: A common TLR1 polymorphism is associated with an increased risk of laboratory-defined neurosyphilis, and common TLR2 and TLR6 polymorphisms are associated with an increased risk of both laboratory- and clinically-defined neurosyphilis. These data suggest that host factors impact the natural history of syphilis.

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