Tumour necrosis factor -308 and -238 promoter polymorphisms are predictors of a null virological response in the treatment of Brazilian hepatitis C patients
Mem. Inst. Oswaldo Cruz
; 109(3): 345-351, 06/2014. tab
Article
in En
| LILACS
| ID: lil-711738
Responsible library:
BR1.1
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.
Key words
Full text:
1
Index:
LILACS
Main subject:
Antiviral Agents
/
Ribavirin
/
Promoter Regions, Genetic
/
Tumor Necrosis Factor-alpha
/
Interferon-alpha
/
Hepacivirus
/
Hepatitis C, Chronic
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Female
/
Humans
/
Male
Country/Region as subject:
America do sul
/
Brasil
Language:
En
Journal:
Mem. Inst. Oswaldo Cruz
Journal subject:
MEDICINA TROPICAL
/
PARASITOLOGIA
Year:
2014
Type:
Article
/
Project document