title: Promoter region polymorphism & expression profile of toll like receptor-3 (TLR-3) gene in chronic hepatitis C virus (HCV) patients from India.
abstract: OBJECTIVE
  Hepatitis C virus (HCV) induces an immune response of the host, manifested by the formation of anti-HCV antibodies mediated by adaptive and innate immunity. Toll-like receptors (TLRs) play a pivotal role in innate immunity system. This study was aimed to investigate the promoter region polymorphism and expression of TLR3 gene in patients with chronic HCV infection.
  
  
  METHODS
  Patients with chronic HCV infection (N=180) and an equal number of age-sex matched controls were included in the study. Patients positive for HCV-RNA were subjected to analysis of TLR3 polymorphism by direct sequencing of PCR products verified by comparing with the sequences reported in the National Centre for Biotechnology Information (NCBI) database (accession number: NT 022792). Expression of TLR3 gene was analyzed by semiquantitative RT-PCR using housekeeping β-actin gene as the internal control.
  
  
  RESULTS
  Polymorphisms at position -288G/A and -705A/G were identified. The results were significant in -705 allele (P=0.004) OR 2.79(1.46-5.42) and were associated with high risk of HCV infection. In silico sequence analysis showed the presence of ectropic viral integration site 1 encoded factor, in which G at -705 results in the loss of this site. The -7C/A polymorphism was not seen in our study cohort. The expression of TLR3 was upregulated in chronic HCV patients compared to healthy controls.
  
  
  CONCLUSIONS
  Polymorphism in the -705A/G allele at the promoter region of the TLR3 gene may predispose individual to HCV infection. However association of TLR3 expression with polymorphism of TLR3 promoter was not found.
authors.affiliation: Department of Medicine, Maulana Azad Medical College, New Delhi, India.
authors.forename: Subhash
authors.initials: S
authors.lastname: Medhi
authors.forename: Manab
authors.initials: M
authors.lastname: Deka
authors.forename: Purabi
authors.initials: P
authors.lastname: Deka
authors.forename: Shyam S
authors.initials: SS
authors.lastname: Swargiary
authors.forename: Rajib K
authors.initials: RK
authors.lastname: Hazam
authors.forename: Manash P
authors.initials: MP
authors.lastname: Sharma
authors.forename: Phani K
authors.initials: PK
authors.lastname: Gumma
authors.forename: Mohammad
authors.initials: M
authors.lastname: Asim
authors.forename: P
authors.initials: P
authors.lastname: Kar
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005260:Female; D016174:Hepacivirus / Q000276:immunology / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000235:genetics* / Q000276:immunology / Q000821:virology; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012189:Retrospective Studies; D051196:Toll-Like Receptor 3 / Q000235:genetics* / Q000378:metabolism*
chemical_list: D051196:Toll-Like Receptor 3