Dataset Information

IFNL4 ss469415590 variant shows similar performance to rs12979860 as predictor of response to treatment against Hepatitis C Virus genotype 1 or 4 in Caucasians.

ABSTRACT:

Objectives

The rs12979860 variant, linked to IL28B gene, predicts sustained viral response (SVR) to pegylated-interferon/ribavirin (pegIFN/RBV) therapy in Hepatitis C Virus genotype 1 or 4 (HCV-1/4)-infected patients. Recently, a functional variant, ss469415590, in linkage disequilibrium (LD) with rs12979860, has been discovered. Our objective was to assess the value of ss469415590 to predict SVR to pegIFN/RBV in Caucasian HCV-1/4-infected individuals and to compare its performance with that of rs12979860.

Methods

272 Caucasian HCV-1/4-infected patients who completed a course of pegIFN/RBV were genotyped for both rs12979860 and ss469415590 markers. Logistic regression models including factors with univariate association with SVR and each genetic marker were elaborated. The area under the receiver operating-characteristic curve (AUROC) was calculated for each model and both were compared.

Results

Both markers were in LD (r2?=?0.82). For rs12979860, 66 (64.0%) CC versus 56 (33.1%) T allele carriers achieved SVR (Adjusted OR?=?4.156, 95%CI?=?2.388-7.232, p?=?4.647×10-7). For ss469415590, 66 (66.0%) TT/TT versus 56 (32.5%) -G allele carriers (Adjusted OR?=?4.783, 95%CI?=?2.714-8.428, p?=?6.153×10-8) achieved SVR. The AUROC of the model including rs12979860 was 0.742 (95%CI?=?0.672-0.813) and of that based on ss469415590 was 0.756 (95%CI?=?0.687-0.826) (p?=?0.780).

Conclusions

The ss469415590 variant shows an equivalent performance to predict SVR to pegIFN/RBV than the rs2979860 in Caucasian HCV-1/4-infected patients.

SUBMITTER: Real LM

PROVIDER: S-EPMC3991683 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

IFNL4 ss469415590 variant shows similar performance to rs12979860 as predictor of response to treatment against Hepatitis C Virus genotype 1 or 4 in Caucasians.

Real Luis M LM Neukam Karin K Herrero Rocío R Guardiola Josep M JM Reiberger Thomas T Rivero-Juarez Antonio A Salazar Juliana J Mandorfer Mattias M Merino Dolores D Soriano Vicente V Rivero Antonio A Macías Juan J Pineda Juan A JA Caruz Antonio A

PloS one 20140418 4

<h4>Objectives</h4>The rs12979860 variant, linked to IL28B gene, predicts sustained viral response (SVR) to pegylated-interferon/ribavirin (pegIFN/RBV) therapy in Hepatitis C Virus genotype 1 or 4 (HCV-1/4)-infected patients. Recently, a functional variant, ss469415590, in linkage disequilibrium (LD) with rs12979860, has been discovered. Our objective was to assess the value of ss469415590 to predict SVR to pegIFN/RBV in Caucasian HCV-1/4-infected individuals and to compare its performance with ...[more]

PMID: 24748394

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Project description:BACKGROUND:Single nucleotide polymorphisms (SNPs) of interleukin-28B (IL28B) have received considerable interest for their association with sustained virological response (SVR) when treating patients of genotype-1 hepatitis C virus (GT1-HCV) chronic infection with pegylated interferon and ribavirin (PegIFN/RBV). This study was to investigate the predictive power of IL28B SNPs for on-treatment responses and SVR in treatment-naïve patients with GT1-HCV chronic infection. METHODOLOGY/PRINCIPAL FINDINGS:We analyzed ten SNPs of IL28B in 191 treatment-naïve patients with GT1-HCV chronic infection who received PegIFN/RBV. In these patients, rapid virological response (RVR), early virological response (EVR) and SVR were achieved in 69.6%, 95.8% and 68.6% of the patients, respectively. Multivariate analysis (odds ratio; 95% confidence interval; P value) indicated age (0.96; 0.93-0.99; 0.012), low baseline viral load (4.65; 2.23-9.66; <0.001) and CC genotype of rs12979860 (7.74; 2.55-23.53; <0.001) but no other SNPs were independent predictors for SVR. In addition, none of the ten SNPs examined were associated with baseline viral load and stages of liver fibrosis. Regarding RVR, low baseline viral load (2.83; 1.40-5.73; 0.004) and CC genotype of rs12979860 (10.52; 3.45-32.04; <0.001) were two critical predictors. As for EVR, only CC genotype of rs12979860 (36.21; 6.68-196.38; <0.001) was the predictor. Similarly, for end of treatment response (ETR), CC genotype of rs12979860 (15.42; 4.62-51.18; <0.001) was the only predictor. For patients with RVR, only low baseline viral load (3.90; 1.57-9.68; 0.003) could predict the SVR. For patients without RVR, only rs12979860 (4.60; 1.13-18.65; 0.033) was the predictor for SVR. CONCLUSIONS/SIGNIFICANCE:rs12979860 is the critical predictor for RVR, EVR, ETR and SVR in treatment-naïve patients of GT1-HCV chronic infection. Furthermore, this SNP is the only predictor for SVR in patients without RVR. These results have provided evidence that rs12979860 is the ideal IL28B SNP for genetic testing in treating patients of GT1-HCV chronic infection.

Dataset Information

IFNL4 ss469415590 variant shows similar performance to rs12979860 as predictor of response to treatment against Hepatitis C Virus genotype 1 or 4 in Caucasians.

Objectives

Methods

Results

Conclusions

Publications

IFNL4 ss469415590 variant shows similar performance to rs12979860 as predictor of response to treatment against Hepatitis C Virus genotype 1 or 4 in Caucasians.

Similar Datasets

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