Association of Toll‐like receptor 4 polymorphism with hepatitis E virus‐infected Indian patients.

Summary: Hepatitis E infection caused by hepatitis E virus (HEV), a major public health concern in developing countries, is responsible for sporadic and epidemic acute viral hepatitis in adults. Pathogenesis of hepatitis E infection is poorly understood. Toll‐like receptors (TLRs) are the key players of innate immunity recognize pathogen‐associated molecular patterns (PAMPs). Previously, we found higher TLR4 expression (at protein and gene level) with impaired cytokine response upon stimulus of PBMCs with LPS in HEV‐infected patients. In view of the earlier observations of the association of polymorphisms in TLR4 genes (A299G, C399T) with liver diseases, we investigated TLR4 polymorphisms in HEV‐infected patients. We observed the significant association of TLR4‐399CC and CT alleles with hepatitis E (both subclinical and acute patients). Carrier frequency of TLR4‐399 CT was lower in patients' categories in comparison with the controls. Higher frequency of allele TLR4‐399C significantly correlated with disease progression. Acute hepatitis E patients showed the higher frequency of CG and TA haplotypes, while the rare haplotype (TG) was more frequent in controls. The other single nucleotide polymorphism (SNP) at TLR4‐299 (A>G) did not show any difference. We report here for the first time the association of TLR4 polymorphism with hepatitis E and suggest that TLR 4 hyporesponsiveness during HEV infection might be related to its polymorphism. [ABSTRACT FROM AUTHOR]