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The Myeloid-Epithelial-Reproductive Tyrosine Kinase (MERTK) rs4374383 Polymorphism Predicts Progression of Liver Fibrosis in Hepatitis C Virus-Infected Patients: A Longitudinal Study

Background: The myeloid-epithelial-reproductive tyrosine kinase (MERTK) is involved in hepatic steatosis, inflammation, and liver fibrosis. Here we evaluated the association between the MERTK rs4374383 single nucleotide polymorphism (SNP) and liver fibrosis progression in hepatitis C virus (HCV)-inf...

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Autores principales: Jiménez-Sousa, María Ángeles, Gómez-Moreno, Ana Zaida, Pineda-Tenor, Daniel, Brochado-Kith, Oscar, Sánchez-Ruano, Juan José, Artaza-Varasa, Tomas, Gómez-Sanz, Alicia, Fernández-Rodríguez, Amanda, Resino, Salvador
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6306820/
https://www.ncbi.nlm.nih.gov/pubmed/30477195
http://dx.doi.org/10.3390/jcm7120473
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author Jiménez-Sousa, María Ángeles
Gómez-Moreno, Ana Zaida
Pineda-Tenor, Daniel
Brochado-Kith, Oscar
Sánchez-Ruano, Juan José
Artaza-Varasa, Tomas
Gómez-Sanz, Alicia
Fernández-Rodríguez, Amanda
Resino, Salvador
author_facet Jiménez-Sousa, María Ángeles
Gómez-Moreno, Ana Zaida
Pineda-Tenor, Daniel
Brochado-Kith, Oscar
Sánchez-Ruano, Juan José
Artaza-Varasa, Tomas
Gómez-Sanz, Alicia
Fernández-Rodríguez, Amanda
Resino, Salvador
author_sort Jiménez-Sousa, María Ángeles
collection PubMed
description Background: The myeloid-epithelial-reproductive tyrosine kinase (MERTK) is involved in hepatic steatosis, inflammation, and liver fibrosis. Here we evaluated the association between the MERTK rs4374383 single nucleotide polymorphism (SNP) and liver fibrosis progression in hepatitis C virus (HCV)-infected patients. Methods: We performed a retrospective study (repeated measures design) in 208 patients who had liver stiffness measurement (LSM), which was assessed using transient elastography. No patient had cirrhosis at baseline (LSM ≥ 12.5 kPa). Results: At baseline, 53.8% were male, the median age was 47.1 years, 13.5% reported a high intake of alcohol, 10.1% were prior injection drug users, 85.3% were infected with HCV genotype 1, and 22.6% had previously failed antiviral therapy (pegylated-interferon-alpha/ribavirin). During a median follow-up of 46.6 months, 26 patients developed cirrhosis. The rs4374383 G carriers had a higher risk of increasing LSM (adjusted arithmetic mean ratio (aAMR) = 1.14; p = 0.006) and a higher likelihood of having an increase in LSM greater than 5 kPa (ΔLSM ≥ 5 kPa) (adjusted odds ratio (aOR) = 2.37; p = 0.029), and greater than 7 kPa (ΔLSM ≥ 7 kPa) (aOR = 3.24; p = 0.032), after controlling for confounding. The SNP’s association with cirrhosis progression was close to statistical significance (aOR = 2.18; p = 0.070). Conclusions: MERTK rs4374383 A carriers had a lower risk of liver fibrosis progression than G carriers, supporting the hypothesis that this SNP seems to have a critical role in the pathogenesis of liver disease in HCV-infected patients.
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spelling pubmed-63068202019-01-02 The Myeloid-Epithelial-Reproductive Tyrosine Kinase (MERTK) rs4374383 Polymorphism Predicts Progression of Liver Fibrosis in Hepatitis C Virus-Infected Patients: A Longitudinal Study Jiménez-Sousa, María Ángeles Gómez-Moreno, Ana Zaida Pineda-Tenor, Daniel Brochado-Kith, Oscar Sánchez-Ruano, Juan José Artaza-Varasa, Tomas Gómez-Sanz, Alicia Fernández-Rodríguez, Amanda Resino, Salvador J Clin Med Article Background: The myeloid-epithelial-reproductive tyrosine kinase (MERTK) is involved in hepatic steatosis, inflammation, and liver fibrosis. Here we evaluated the association between the MERTK rs4374383 single nucleotide polymorphism (SNP) and liver fibrosis progression in hepatitis C virus (HCV)-infected patients. Methods: We performed a retrospective study (repeated measures design) in 208 patients who had liver stiffness measurement (LSM), which was assessed using transient elastography. No patient had cirrhosis at baseline (LSM ≥ 12.5 kPa). Results: At baseline, 53.8% were male, the median age was 47.1 years, 13.5% reported a high intake of alcohol, 10.1% were prior injection drug users, 85.3% were infected with HCV genotype 1, and 22.6% had previously failed antiviral therapy (pegylated-interferon-alpha/ribavirin). During a median follow-up of 46.6 months, 26 patients developed cirrhosis. The rs4374383 G carriers had a higher risk of increasing LSM (adjusted arithmetic mean ratio (aAMR) = 1.14; p = 0.006) and a higher likelihood of having an increase in LSM greater than 5 kPa (ΔLSM ≥ 5 kPa) (adjusted odds ratio (aOR) = 2.37; p = 0.029), and greater than 7 kPa (ΔLSM ≥ 7 kPa) (aOR = 3.24; p = 0.032), after controlling for confounding. The SNP’s association with cirrhosis progression was close to statistical significance (aOR = 2.18; p = 0.070). Conclusions: MERTK rs4374383 A carriers had a lower risk of liver fibrosis progression than G carriers, supporting the hypothesis that this SNP seems to have a critical role in the pathogenesis of liver disease in HCV-infected patients. MDPI 2018-11-23 /pmc/articles/PMC6306820/ /pubmed/30477195 http://dx.doi.org/10.3390/jcm7120473 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jiménez-Sousa, María Ángeles
Gómez-Moreno, Ana Zaida
Pineda-Tenor, Daniel
Brochado-Kith, Oscar
Sánchez-Ruano, Juan José
Artaza-Varasa, Tomas
Gómez-Sanz, Alicia
Fernández-Rodríguez, Amanda
Resino, Salvador
The Myeloid-Epithelial-Reproductive Tyrosine Kinase (MERTK) rs4374383 Polymorphism Predicts Progression of Liver Fibrosis in Hepatitis C Virus-Infected Patients: A Longitudinal Study
title The Myeloid-Epithelial-Reproductive Tyrosine Kinase (MERTK) rs4374383 Polymorphism Predicts Progression of Liver Fibrosis in Hepatitis C Virus-Infected Patients: A Longitudinal Study
title_full The Myeloid-Epithelial-Reproductive Tyrosine Kinase (MERTK) rs4374383 Polymorphism Predicts Progression of Liver Fibrosis in Hepatitis C Virus-Infected Patients: A Longitudinal Study
title_fullStr The Myeloid-Epithelial-Reproductive Tyrosine Kinase (MERTK) rs4374383 Polymorphism Predicts Progression of Liver Fibrosis in Hepatitis C Virus-Infected Patients: A Longitudinal Study
title_full_unstemmed The Myeloid-Epithelial-Reproductive Tyrosine Kinase (MERTK) rs4374383 Polymorphism Predicts Progression of Liver Fibrosis in Hepatitis C Virus-Infected Patients: A Longitudinal Study
title_short The Myeloid-Epithelial-Reproductive Tyrosine Kinase (MERTK) rs4374383 Polymorphism Predicts Progression of Liver Fibrosis in Hepatitis C Virus-Infected Patients: A Longitudinal Study
title_sort myeloid-epithelial-reproductive tyrosine kinase (mertk) rs4374383 polymorphism predicts progression of liver fibrosis in hepatitis c virus-infected patients: a longitudinal study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6306820/
https://www.ncbi.nlm.nih.gov/pubmed/30477195
http://dx.doi.org/10.3390/jcm7120473
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