Low-density lipoprotein receptor variants are associated with spontaneous and treatment-induced recovery from hepatitis C virus infection.
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.
Mas Marques
Andreas
A
Robert Koch-Institut, Berlin, Germany.
Mueller
Tobias
T
Welke
Justus
J
Taube
Stefan
S
Sarrazin
Christoph
C
Wiese
Manfred
M
Halangk
Juliane
J
Witt
Heiko
H
Ahlenstiel
Golo
G
Spengler
Ulrich
U
Goebel
Uwe
U
Schott
Eckart
E
Weich
Viola
V
Schlosser
Beate
B
Wasmuth
Hermann E
HE
Lammert
Frank
F
Berg
Thomas
T
Schreier
Eckart
E
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
D020413:3' Untranslated Regions; D000998:Antiviral Agents; D011973:Receptors, LDL; D007372:Interferons