Low-density lipoprotein receptor variants are associated with spontaneous and treatment-induced recovery from hepatitis C virus infection

• Published in: Infection, genetics and evolution genetics and evolution, 2009-09, Vol.9 (5), p.847-852
• Main Authors: Mas Marques, Andreas, Mueller, Tobias, Welke, Justus, Taube, Stefan, Sarrazin, Christoph, Wiese, Manfred, Halangk, Juliane, Witt, Heiko, Ahlenstiel, Golo, Spengler, Ulrich, Goebel, Uwe, Schott, Eckart, Weich, Viola, Schlosser, Beate, Wasmuth, Hermann E., Lammert, Frank, Berg, Thomas, Schreier, Eckart
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions; Adult; Aged; Antiviral Agents - therapeutic use; Antiviral therapy; Case-Control Studies; Cross-Sectional Studies; Exons; Female; Genotype; HCV infection; Hepatitis C virus; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - genetics; Humans; Interferon; Interferons - therapeutic use; LDL receptor; LDLR; Logistic Models; Male; Middle Aged; Multivariate Analysis; Polymorphism, Single Nucleotide; Receptors, LDL - genetics; Remission Induction; Remission, Spontaneous; Ribavirin; Self-limited infection; Single-nucleotide alteration; Spontaneous recovery; Virologic response; Young Adult
• ISSN: 1567-1348; 1567-7257
• DOI: 10.1016/j.meegid.2009.05.002

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.