Lack of Association of TLR1 and TLR5 Coding Variants with Mortality in a Large Multicenter Cohort of Melioidosis Patients

TL;DR

This study found no link between two genetic variants in TLR1 and TLR5 and mortality or bacteremia in a large group of melioidosis patients.

Contribution

The study externally validates previous findings in a larger multicenter cohort, showing no association of TLR1 and TLR5 variants with melioidosis outcomes.

Findings

Genotype frequencies of rs76600635 and rs5744168 did not differ by bacteremia status or 28-day mortality.

Neither variant showed significant associations with bacteremia or mortality under a dominant genetic model.

No associations were found for either variant with 1-year mortality.

Abstract

Melioidosis, infection caused by Burkholderia pseudomallei, is characterized by robust innate immune responses. We have previously reported associations of TLR1 single nucleotide missense variant rs76600635 with mortality and of TLR5 nonsense variant rs5744168 with both bacteremia and mortality in single-center studies of patients with melioidosis in northeastern Thailand. The objective of this study was to externally validate the associations of rs76600635 and rs5744168 with bacteremia and mortality in a large multicenter cohort of melioidosis patients. We genotyped rs76600635 and rs5744168 in 1,338 melioidosis patients enrolled in a prospective parent cohort study conducted at nine hospitals in northeastern Thailand. The genotype frequencies of rs76600635 did not differ by bacteremia status (P = 0.27) or 28-day mortality (P = 0.84). The genotype frequencies of rs5744168 did not differ by either bacteremia status (P = 0.46) or 28-day mortality (P = 0.10). Assuming a dominant genetic model, there was no association of the rs76600635 variant with bacteremia (adjusted odds ratio [OR], 0.75; 95% CI, 0.54–1.04, P = 0.08) or 28-day mortality (adjusted OR, 0.96; 95% CI, 0.71–1.28, P = 0.77). There was no association of the rs5744168 variant with bacteremia (adjusted OR, 1.24; 95% CI, 0.76–2.03, P = 0.39) or 28-day mortality (adjusted OR, 1.22; 95% CI, 0.83–1.79, P = 0.21). There was also no association of either variant with 1-year mortality. We conclude that in a large multicenter cohort of patients hospitalized with melioidosis in northeastern Thailand, neither TLR1 missense variant rs76600635 nor TLR5 nonsense variant rs5744168 is associated with bacteremia or mortality.