An efficient immune response against hepatitis C virus (HCV) is necessary to 
clear infection. As HCV is a single-stranded RNA virus, a role for TLR7 in the 
immune response against HCV is possible, and early clinical studies have 
demonstrated an antiviral effect of TLR7 stimulation. We tested the hypothesis 
that genetic variations of TLR7 are associated with chronic HCV-infection and 
outcome of therapy. The prevalence of three TLR7 variations was analysed in 978 
patients with chronic HCV-infection, 898 patients with chronic liver disease of 
other aetiologies, and in 203 healthy controls. The prevalence of TLR7 
variations was correlated with the response to interferon-alpha-based treatment 
in 544 patients with chronic HCV-infection. We analysed TLR7 polymorphisms by 
melting curve analysis and reconstructed haplotypes. The c.32A>T variation was 
over-represented in female patients with chronic HCV-infection compared to 
patients with other chronic liver diseases and to healthy controls (P < 0.05). 
In contrast, c.2403 G>A was less prevalent in male patients with chronic 
HCV-infection (P < 0.05). No association was observed for the third variant, 
c.1-120T>G. Haplotype analysis confirmed the differential distribution of TLR7 
variants between the groups. Within the group of female patients with chronic 
HCV-infection, c.32T was predictive of an unfavourable outcome of 
interferon-alpha therapy (P < 0.05). This study reports the association of TLR7 
variants with chronic HCV-infection and with the response to interferon-alpha 
therapy in patients with chronic HCV-infection. Our results suggest that 
variations of TLR7 impair the immune response to HCV and imply a gender-specific 
effect of this X-chromosomal variation.