Core amino acid variation at position 110 is associated with sustained virological response in Caucasian patients with chronic hepatitis C virus 1b infection

Authors
Di Lello, Federico Alejandro; Mira, José Antonio; Neukam, Karin; Parra Sánchez, Manuel; Guelfo, Javier R.; Cifuentes, Celia; Macias, Juan; Palomares, José Carlos; Gomez Mateos, Jesús; Pineda, Juan Antonio; Real, Luis M.
Publication Year
2014
Language
English
Format
article
Status
Published version
Description
The aim of this study was to analyze the impact of core variations on sustained virological response (SVR) to pegylated interferon plus ribavirin (PEG-IFN/RBV) and its association with predictive factors of response in Caucasian patients infected with genotype 1 hepatitis C virus (HCV-1). Full-length core sequences were analyzed in 100 Caucasian HCV-1-infected patients who received therapy with PEG-IFN/RBV. The associations between variations in the core protein and SVR, as well as with predictors of SVR, were analyzed. Variations at core 62, 70 and 110 were selected as candidates. There were almost no variations at these positions among patients harboring HCV-1a. However, they were identified in 10 (30.3 %), 21 (63.6 %) and 13 (39.4 %) subjects with HCV-1b, respectively. Among the HCV-1b patients, 39.1 % individuals carrying core R62 and 70 % subjects with core R62G showed SVR (p = 0.141), and 66.7 % of HCV-1b patients harboring core R70 and 38.1 % with core R70Q achieved SVR (p = 0.157), whereas the rate of SVR was 70 % for individuals with core T110 and 15.4 % for those with core T110N (p = 0.004). No statistical interaction between core variations and IL28B genotype was observed. Patients with R70 showed higher median (interquartile range) baseline plasma levels of low-density-lipoprotein cholesterol (LDL-C) than those with R70Q (96 [86-118] mg/dL vs. 76 [54-88] mg/dL, p = 0.014). We concluded that a substitution at core 110 is associated with a lower rate of SVR in Caucasian HCV-1b-infected patients receiving PEG-IFN/RBV. Furthermore, the variation at the core 70 position is related to plasma levels of LDL-C in these patients.
Fil: Di Lello, Federico Alejandro. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Universitario de Valme; España
Fil: Mira, José Antonio. Hospital Universitario de Valme; España
Fil: Neukam, Karin. Hospital Universitario de Valme; España
Fil: Parra Sánchez, Manuel. Hospital Universitario de Valme; España
Fil: Guelfo, Javier R.. Hospital Universitario de Valme; España
Fil: Cifuentes, Celia. Hospital Universitario de Valme; España
Fil: Macias, Juan. Hospital Universitario de Valme; España
Fil: Palomares, José Carlos. Hospital Universitario de Valme; España
Fil: Gomez Mateos, Jesús. Hospital Universitario de Valme; España
Fil: Pineda, Juan Antonio. Hospital Universitario de Valme; España
Fil: Real, Luis M.. Hospital Universitario de Valme; España
Subject
HEPATITIS C VIRUS
MUTATION
TREATMENT
CORE
Gastroenterología y Hepatología
Medicina Clínica
CIENCIAS MÉDICAS Y DE LA SALUD
Access level
Restricted access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/15808