| Abstract: | Certain host single nucleotide polymorphisms (SNPs) affect the likelihood of a
sustained virological response (SVR) to treatment in subjects infected with hepatitis
C virus (HCV). SNPs in the promoters of interleukin (IL)-10 (-1082 A/G, rs1800896),
myxovirus resistance protein 1 (-123 C/A, rs17000900 and -88 G/T, rs2071430) and
tumour necrosis factor (TNF) (-308 G/A, rs1800629 and -238 G/A, rs361525) genes and
the outcome of PEGylated α-interferon plus ribavirin therapy were investigated. This
analysis was performed in 114 Brazilian, HCV genotype 1-infected patients who had a
SVR and in 85 non-responders and 64 relapsers. A significantly increased risk of
having a null virological response was observed in patients carrying at least one A
allele at positions -308 odds ratios (OR) = 2.58, 95% confidence intervals (CI) =
1.44-4.63, p = 0.001] or -238 (OR = 7.33, 95% CI = 3.59-14.93, p < 0.001) in the
TNF promoter. The risk of relapsing was also elevated (-308: OR = 2.87, 95% CI =
1.51-5.44, p = 0.001; -238: OR = 4.20, 95% CI = 1.93-9.10, p < 0.001). Multiple
logistic regression of TNF diplotypes showed that patients with at least two copies
of the A allele had an even higher risk of having a null virological response (OR =
16.43, 95% CI = 5.70-47.34, p < 0.001) or relapsing (OR = 6.71, 95% CI =
2.18-20.66, p = 0.001). No statistically significant association was found between
the other SNPs under study and anti-HCV therapy response. |
