title: Low-density lipoprotein receptor variants are associated with spontaneous and treatment-induced recovery from hepatitis C virus infection.
abstract: Low-density lipoprotein receptor (LDLR) is involved in the entry of hepatitis C virus (HCV) in host cells. We investigated whether three single-nucleotide alterations within LDLR might be associated with the course of hepatitis C infection and response to antiviral therapy. We enrolled 651 individuals with chronic HCV infection who had received interferon-based combination therapy, 174 individuals with self-limited HCV infection, and 516 healthy controls. LDLR c.1171G>A, c.1413G>A, and c.*52G>A genotyping was performed by real-time PCR-based assays. HCV genotype 1-infected individuals who were homozygous for 3'UTR c.*52G were at increased risk for virologic non-response to antiviral therapy compared to virologic responders (66.3% vs. 51.0%, p=0.001). Furthermore, compared to healthy controls, self-limited HCV genotype 1 infection was significantly associated with c.1171A (15.1% vs. 6.6%, p=0.006) and negatively associated with c.1413G>A heterozygosity (33.0% vs. 46.1%, p=0.023). The data indicate that LDLR alterations are correlated with response to interferon-based combination therapy and with self-limitation of HCV 1 infection.
authors.affiliation: Robert Koch-Institut, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Mas Marques
authors.forename: Tobias
authors.initials: T
authors.lastname: Mueller
authors.forename: Justus
authors.initials: J
authors.lastname: Welke
authors.forename: Stefan
authors.initials: S
authors.lastname: Taube
authors.forename: Christoph
authors.initials: C
authors.lastname: Sarrazin
authors.forename: Manfred
authors.initials: M
authors.lastname: Wiese
authors.forename: Juliane
authors.initials: J
authors.lastname: Halangk
authors.forename: Heiko
authors.initials: H
authors.lastname: Witt
authors.forename: Golo
authors.initials: G
authors.lastname: Ahlenstiel
authors.forename: Ulrich
authors.initials: U
authors.lastname: Spengler
authors.forename: Uwe
authors.initials: U
authors.lastname: Goebel
authors.forename: Eckart
authors.initials: E
authors.lastname: Schott
authors.forename: Viola
authors.initials: V
authors.lastname: Weich
authors.forename: Beate
authors.initials: B
authors.lastname: Schlosser
authors.forename: Hermann E
authors.initials: HE
authors.lastname: Wasmuth
authors.forename: Frank
authors.initials: F
authors.lastname: Lammert
authors.forename: Thomas
authors.initials: T
authors.lastname: Berg
authors.forename: Eckart
authors.initials: E
authors.lastname: Schreier
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005091:Exons; D005260:Female; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D011973:Receptors, LDL / Q000235:genetics*; D012074:Remission Induction; D012075:Remission, Spontaneous; D055815:Young Adult
chemical_list: D020413:3' Untranslated Regions; D000998:Antiviral Agents; D011973:Receptors, LDL; D007372:Interferons