Study of Single Nucleotide Polymorphisms in Endosomal Toll-Like Receptors-3, 7, and 9 Genes in Patients With Dengue: A Case-Control Study.

Abstract

IntroductionThe endosomal toll-like receptors (TLR) TLR3, TLR7, and TLR9 are localized in immune cells, recognize the viral pattern associated molecular pattern (PAMPs), and start signaling cascades for immune defense response and genetic factor is known to affect the dengue virus infection therefore in our study we study the association of endosomal Toll-like receptors 3 polymorphism rs3775291, rs3775290, and rs3775296 with rs179008 A/T and rs179009C/T polymorphisms of TLR7 and rs187084 (C/T), rs5743836 (C/T) of TLR9 gene with dengue and controls.Materials and methodsNinety-eight cases of dengue virus (DV) infection and 98 healthy controls were enrolled. Clinical details were recorded and cases were classified as severe or non-severe dengue, based on WHO 2009 classification. Genotypes were determined by Sanger sequencing using the genetic analyzer.ResultsAn increased risk of DV infection was observed in cases as compared to controls, with TLR 3 rs3775291 CT genotype (OR = 4.34, P-value: 0.031, CI = 1.14-16.5), Likewise in TLR7 rs179008 AT (OR = 2.12, P-value: 0.034, CI = 1.06-4.26) and rs179009 CT (OR = 2.04, P-value: 0.040, CI = 1.03-4.05) same as in TLR9 rs187084 CT (OR = 1.97, P-value: 0.046, CI = 1.013-3.84) and rs5743836 (OR = 2.38, P-value: 0.009, CI = 1.24-5.57). In the above polymorphisms, mutant allele was observed in a significantly higher number in cases. The values are: for TLR3 rs3775291 T allele (OR 2.167, CI = 1.3-3.61, P-value: 0.003). TLR7 rs179008 T allele (OR 1.90, P-value: 0.021, CI = 1.07-3.35) and in TLR9 rs187084 (OR 1.91, P-value: 0.014, CI = 1.137-3.24) rs5743836 (OR 2.29, P-value: 0.0018, CI = 1.36-3.87). No significant association was observed in the genotypic frequency of severe versus non-severe dengue.ConclusionTLR3, 7, and 9 gene polymorphism might confer host genetic susceptibility to dengue in the North Indian population