title: Association of low-density lipoprotein receptor genotypes with hepatitis C viral load.
abstract: Several data suggest that low-density lipoprotein receptor (LDLR) is a co-receptor for hepatitis C virus (HCV). Soluble LDLR can inhibit HCV infectivity; greater plasma low-density lipoprotein levels are associated with treatment success; LDLR genotypes have a synergistic impact on the likelihood of achieving SVR with Peg-IFN plus RBV, as well as on viral kinetics after starting treatment. The objective of this study was to assess the impact of genetic polymorphisms in genes related to cholesterol synthesis and transport pathways on pre-treatment plasma HCV viral load (VL). A total of 442 patients infected with HCV and treatment naive were prospectively recruited. One hundred forty-four SNPs located in 40 genes from the cholesterol synthesis/transport and IL28B were genotyped and analyzed for genetic association with pre-treatment plasma HCV VL. SNPs rs1433099 and rs2569540 of LDLR showed association with plasma HCV VL (P=4 × 10(-4) and P=2 × 10(-3)) in patients infected with genotypes 1 and 4. A haplotype including the last three exons of LDLR showed association with the cutoff level of 600 000 IU ml(-1) VL for genotypes 1 and 4 (OR=0.27; P=8 × 10(-6)), as well as a quantitative VL (mean±s.d.: 6.19±0.9 vs CC+CG 5.58±1.1 logIU ml(-1), P=8 × 10(-5)). LDLR genotypes are a major genetic factor influencing HCV VL in patients infected with genotypes 1 and 4.
authors.affiliation: Immunogenetics Unit, Department of Experimental, Biology Faculty of Sciences, Universidad de Jaén, Jaén, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Caruz
authors.affiliation: Unit of Infectious Diseases and Microbiology, Hospital Universitario de Valme, Instituto de Biomedicina de Sevilla (IBiS), Seville, Spain.
authors.forename: K
authors.initials: K
authors.lastname: Neukam
authors.affiliation: Unit of Infectious Diseases, Maimonides Institute for Biomedical Research (IMIBIC), Hospital Universitario Reina Sofía, Córdoba, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Rivero-Juárez
authors.affiliation: Immunogenetics Unit, Department of Experimental, Biology Faculty of Sciences, Universidad de Jaén, Jaén, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Herrero
authors.affiliation: Unit of Infectious Diseases and Microbiology, Hospital Universitario de Valme, Instituto de Biomedicina de Sevilla (IBiS), Seville, Spain.
authors.forename: L M
authors.initials: LM
authors.lastname: Real
authors.affiliation: Unit of Infectious Diseases, Maimonides Institute for Biomedical Research (IMIBIC), Hospital Universitario Reina Sofía, Córdoba, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Camacho
authors.affiliation: Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Barreiro
authors.affiliation: Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Labarga
authors.affiliation: Unit of Infectious Diseases, Maimonides Institute for Biomedical Research (IMIBIC), Hospital Universitario Reina Sofía, Córdoba, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Rivero
authors.affiliation: Unit of Infectious Diseases and Microbiology, Hospital Universitario de Valme, Instituto de Biomedicina de Sevilla (IBiS), Seville, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: Pineda
mesh_terms: D000328:Adult; D002784:Cholesterol / Q000235:genetics / Q000378:metabolism; D060085:Coinfection; D005091:Exons; D005260:Female; D015658:HIV Infections / Q000235:genetics / Q000821:virology; D006239:Haplotypes; D016174:Hepacivirus / Q000235:genetics* / Q000472:pathogenicity; D006526:Hepatitis C / Q000235:genetics* / Q000821:virology*; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011973:Receptors, LDL / Q000235:genetics*; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D002784:Cholesterol; D007372:Interferons; D007378:Interleukins; D011973:Receptors, LDL; C000624353:interferon-lambda, human; D000095022:Interferon Lambda