title: Toll-like receptor 8 (TLR8) polymorphisms are associated with non-progression of chronic hepatitis C in HIV/HCV coinfected patients.
abstract: Toll-like receptor 8 (TLR8) polymorphisms have been related to hepatitis C virus (HCV) infection. The aim was to estimate the association of TLR8 polymorphisms with HCV-related outcomes in HIV/HCV coinfected patients. We performed a cross-sectional study of 220 patients who underwent a liver biopsy. TLR8 polymorphisms were genotyped using GoldenGate® assay. The outcome variables were non-fibrosis (F0), mild-inflammation (A0/A1), and non-steatosis [fatty hepatocytes (FH) <10%]. Logistic regression analysis was used to compare the outcome variables according to TLR8 polymorphisms. Four polymorphisms were analyzed (rs1013151, rs5744069, rs17256081 and rs3764880rs1013151). Female patients had higher frequency of TLR8 major alleles at rs17256081 and rs101315, and minor alleles at rs3764880 and rs5744069. Male patients had higher frequency of TLR8 minor alleles except for rs3764880, where major alleles were higher (p<0.01). Two TLR8 polymorphisms (rs1013151 and rs5744069) were significantly associated with non-fibrosis (F0) [adjusted odds ratio (aOR)=4.42 (95% of confidence interval (95%CI)=1.54; 12.68) (p=0.006) and aOR=4.76 (95%CI=1.69; 13.37) (p=0.003); respectively]. When data were stratified by gender, rs1013151 and rs5744069 polymorphisms remained significant for male patients [adjusted odds ratio (aOR)=4.49 (95%CI=1.08; 18.62) (p=0.039) and aOR=6.17 (95%CI=1.45; 26.20) (p=0.014); respectively]. When data were stratified by major HCV genotypes, patients infected with HCV genotype 1 (GT1) had significant values for both rs1013151 and rs5744069 polymorphisms [aOR=5.79 (95%CI=1.44; 23.32) (p=0.013) and aOR=8.01 (95%CI=2.16; 35.65) (p=0.005); respectively]. Finally, none of the TLR8 polymorphisms were significantly associated with mild-inflammation or non-steatosis. In conclusion, TLR8 polymorphisms seem to be related to non-progression of liver fibrosis in HIV/HCV coinfected patients, particularly in males and those patients infected with GT1.
authors.affiliation: Viral Infection and Immunity Unit, National Centre for Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: Amanda
authors.initials: A
authors.lastname: Fernández-Rodríguez
authors.affiliation: Infectious Diseases and HIV Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Berenguer
authors.affiliation: Viral Infection and Immunity Unit, National Centre for Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: María A
authors.initials: MA
authors.lastname: Jiménez-Sousa
authors.affiliation: Viral Infection and Immunity Unit, National Centre for Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: García-Álvarez
authors.affiliation: Infectious Diseases and HIV Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Aldámiz-Echevarría
authors.affiliation: Viral Infection and Immunity Unit, National Centre for Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Pineda-Tenor
authors.affiliation: Infectious Diseases and HIV Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Diez
authors.affiliation: Bioinformatics Unit, National Centre for Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: de la Barrera
authors.affiliation: Biomedical Research Foundation, Hospital General Universitario "Gregorio Marañón", Madrid, Spain.
authors.forename: Jose Mª
authors.initials: JM
authors.lastname: Bellon
authors.affiliation: Viral Infection and Immunity Unit, National Centre for Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Briz
authors.affiliation: Viral Infection and Immunity Unit, National Centre for Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain. Electronic address: sresino@isciii.es.
authors.forename: Salvador
authors.initials: S
authors.lastname: Resino
mesh_terms: D000328:Adult; D000483:Alleles; D001706:Biopsy; D060085:Coinfection; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015658:HIV Infections / Q000235:genetics* / Q000821:virology*; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000235:genetics* / Q000473:pathology / Q000821:virology*; D006801:Humans; D015810:Linkage Disequilibrium; D008099:Liver / Q000473:pathology / Q000821:virology; D008297:Male; D063868:Patient Outcome Assessment; D020641:Polymorphism, Single Nucleotide; D051200:Toll-Like Receptor 8 / Q000235:genetics*; D019562:Viral Load
chemical_list: D051200:Toll-Like Receptor 8
keywords: AIDS; Chronic hepatitis C; Fibrosis; Liver biopsy; SNPs; TLR8