Association of Toll-like Receptor 9 (TLR9) Alterations in Malaria Susceptibility and Severity: A Tribal Population Based Study in the Malaria Endemic State of Assam, India.

摘要

Background: Toll-like receptors (TLRs) are group oftrans-membrane proteins that recognizes specificmolecular pattern and activates the downstreamcytokines for the efficient clearance of pathogens.Objectives: To evaluate the role of TLR9 1486T/Cpolymorphism and its association with the malarialpathogenicity and severity. Material and Methods:Present study was a cohort based study and a totalnumber of 150 samples were drawn from three majortribal population group's viz., Karbi, Dimasa and Boro-Kachari. TLR9 (1486T/C) gene polymorphism wasassessed using polymerase chain reaction-restrictionfragment length polymorphism (PCR-RFLP)technique. Differential TLR9 m-RNA expression wasassessed using Real time PCR (RT-PCR). Results:TLR9 1486T/C genotype variant showed increasedrisk for the susceptibility of malarial infection(p=0.141) compared to controls. The variant genotypeshowed significant increased risk with susceptibility tosevere malaria infection (p=0.047) compared touncomplicated malaria (UC-M). TLR9 mRNA levelexpression showed up-regulation in UC-M comparedto controls. Decreased TLR9 expression was found inSM cases compared to UC-M (p=0.312). Significantdown-regulation of TLR9 gene was found in UC-Mwith variant C genotype cases compared to wild types(p= 0.039). Conclusion: Our finding indicates theassociation of the TLR9 gene polymorphism andlinked differential expression modulation in thedevelopment of malarial pathogenicity.