X-linked polymorphisms in TLR7 and TLR8 genes are associated with protection against Chikungunya fever

BACKGROUND Chikungunya virus (CHIKV) causes an infection that leads to the activation of the innate immune response, triggering receptor pathways such as toll-like receptors (TLRs). OBJECTIVE The present study aimed to investigate the association of single nucleotide polymorphisms (SNPs) in genes encoding toll-like receptors 3, 7, and 8 and IRF5 in susceptibility to CHIKV infection and persistent joint pain. METHODS A case-control study was carried out. The study included 121 symptomatic cases, 29 asymptomatic cases, and 182 healthy controls matched for age and sex. Polymorphisms were identified by TaqMan® SNP Genotyping assays. FINDINGS The G allele of the TLR7 variant (rs3853839 G/C) and the G allele of TLR8 (rs3764879 G/C) were associated with protection against CHIKV infection [adjusted odd ratio (OR) = 0.64; p = 0.02 and adjusted OR = 0.54; p = 0.001, respectively]. Moreover, individuals who presented the G allele in the rs3764879 variant have a greater chance of developing the asymptomatic form (adjusted OR =2.88; p =0.004). The development of persistent joint pain was not associated with any investigated SNPs in positive anti-CHIKV IgG individuals. MAIN CONCLUSIONS This study identified TLR7 and TLR8 gene polymorphisms as protective factors for Chikungunya infection.