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Impact of DARC rs12075 Variants on Liver Fibrosis Progression in Patients with Chronic Hepatitis C: A Retrospective Study

The Duffy antigen receptor for chemokines (DARC) rs12075 polymorphism regulates leukocyte trafficking and proinflammatory chemokine homeostasis. Hepatitis C virus (HCV)-mediated liver fibrosis is associated with an uncontrolled inflammatory response. In this study, we evaluate the association betwee...

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Autores principales: Jiménez-Sousa, María Ángeles, Gómez-Moreno, Ana Zaida, Pineda-Tenor, Daniel, Sánchez-Ruano, Juan José, Artaza-Varasa, Tomas, Martin-Vicente, María, Fernández-Rodríguez, Amanda, Martínez, Isidoro, Resino, Salvador
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523653/
https://www.ncbi.nlm.nih.gov/pubmed/30970632
http://dx.doi.org/10.3390/biom9040143
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author Jiménez-Sousa, María Ángeles
Gómez-Moreno, Ana Zaida
Pineda-Tenor, Daniel
Sánchez-Ruano, Juan José
Artaza-Varasa, Tomas
Martin-Vicente, María
Fernández-Rodríguez, Amanda
Martínez, Isidoro
Resino, Salvador
author_facet Jiménez-Sousa, María Ángeles
Gómez-Moreno, Ana Zaida
Pineda-Tenor, Daniel
Sánchez-Ruano, Juan José
Artaza-Varasa, Tomas
Martin-Vicente, María
Fernández-Rodríguez, Amanda
Martínez, Isidoro
Resino, Salvador
author_sort Jiménez-Sousa, María Ángeles
collection PubMed
description The Duffy antigen receptor for chemokines (DARC) rs12075 polymorphism regulates leukocyte trafficking and proinflammatory chemokine homeostasis. Hepatitis C virus (HCV)-mediated liver fibrosis is associated with an uncontrolled inflammatory response. In this study, we evaluate the association between the DARC rs12075 polymorphism and liver stiffness progression in HCV-infected patients. We carried out a retrospective cohort study (repeated measures design) in 208 noncirrhotic patients with chronic hepatitis C (CHC) who had at least two liver stiffness measurements (LSM) with a separation of at least 12 months. We used generalized linear models to analyze the association between DARC rs12075 polymorphism and outcome variables. During a follow-up of 46.6 months, the percentage of patients with stages of fibrosis F0/F1 decreased (p < 0.001), while LSM values and the percentage of patients with cirrhosis increased (p < 0.001). This pattern of changes was maintained in each of the groups of patients analyzed according to their rs12075 genotypes (AA or AG/GG). However, the variations in liver stiffness characteristics were lower in patients with the rs12075 AG/GG genotype (AG/GG versus AA). Thereby, in the adjusted analysis, patients with the rs12075 AG/GG genotype had a lower risk of an increased value of LSM2/LSM1 arithmetic mean ratio (AMR = 0.83; p = 0.001) and of an increase in LSM ≥ 5 kPa (odds ratio (OR) = 0.28; p = 0.009). Besides, patients with rs12075 AG/GG had a lower risk of cirrhosis progression (OR = 0.24; p = 0.009). No significant associations were found for an increase in LSM ≥ 10 kPa. We found an association between the DARC rs12075 single nucleotide polymorphism (SNP) and CHC progression. Specifically, patients with the DARC rs12075 AG/GG genotype had a lower risk of liver fibrosis progression and development of cirrhosis.
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spelling pubmed-65236532019-06-03 Impact of DARC rs12075 Variants on Liver Fibrosis Progression in Patients with Chronic Hepatitis C: A Retrospective Study Jiménez-Sousa, María Ángeles Gómez-Moreno, Ana Zaida Pineda-Tenor, Daniel Sánchez-Ruano, Juan José Artaza-Varasa, Tomas Martin-Vicente, María Fernández-Rodríguez, Amanda Martínez, Isidoro Resino, Salvador Biomolecules Article The Duffy antigen receptor for chemokines (DARC) rs12075 polymorphism regulates leukocyte trafficking and proinflammatory chemokine homeostasis. Hepatitis C virus (HCV)-mediated liver fibrosis is associated with an uncontrolled inflammatory response. In this study, we evaluate the association between the DARC rs12075 polymorphism and liver stiffness progression in HCV-infected patients. We carried out a retrospective cohort study (repeated measures design) in 208 noncirrhotic patients with chronic hepatitis C (CHC) who had at least two liver stiffness measurements (LSM) with a separation of at least 12 months. We used generalized linear models to analyze the association between DARC rs12075 polymorphism and outcome variables. During a follow-up of 46.6 months, the percentage of patients with stages of fibrosis F0/F1 decreased (p < 0.001), while LSM values and the percentage of patients with cirrhosis increased (p < 0.001). This pattern of changes was maintained in each of the groups of patients analyzed according to their rs12075 genotypes (AA or AG/GG). However, the variations in liver stiffness characteristics were lower in patients with the rs12075 AG/GG genotype (AG/GG versus AA). Thereby, in the adjusted analysis, patients with the rs12075 AG/GG genotype had a lower risk of an increased value of LSM2/LSM1 arithmetic mean ratio (AMR = 0.83; p = 0.001) and of an increase in LSM ≥ 5 kPa (odds ratio (OR) = 0.28; p = 0.009). Besides, patients with rs12075 AG/GG had a lower risk of cirrhosis progression (OR = 0.24; p = 0.009). No significant associations were found for an increase in LSM ≥ 10 kPa. We found an association between the DARC rs12075 single nucleotide polymorphism (SNP) and CHC progression. Specifically, patients with the DARC rs12075 AG/GG genotype had a lower risk of liver fibrosis progression and development of cirrhosis. MDPI 2019-04-09 /pmc/articles/PMC6523653/ /pubmed/30970632 http://dx.doi.org/10.3390/biom9040143 Text en © 2019 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
Sánchez-Ruano, Juan José
Artaza-Varasa, Tomas
Martin-Vicente, María
Fernández-Rodríguez, Amanda
Martínez, Isidoro
Resino, Salvador
Impact of DARC rs12075 Variants on Liver Fibrosis Progression in Patients with Chronic Hepatitis C: A Retrospective Study
title Impact of DARC rs12075 Variants on Liver Fibrosis Progression in Patients with Chronic Hepatitis C: A Retrospective Study
title_full Impact of DARC rs12075 Variants on Liver Fibrosis Progression in Patients with Chronic Hepatitis C: A Retrospective Study
title_fullStr Impact of DARC rs12075 Variants on Liver Fibrosis Progression in Patients with Chronic Hepatitis C: A Retrospective Study
title_full_unstemmed Impact of DARC rs12075 Variants on Liver Fibrosis Progression in Patients with Chronic Hepatitis C: A Retrospective Study
title_short Impact of DARC rs12075 Variants on Liver Fibrosis Progression in Patients with Chronic Hepatitis C: A Retrospective Study
title_sort impact of darc rs12075 variants on liver fibrosis progression in patients with chronic hepatitis c: a retrospective study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523653/
https://www.ncbi.nlm.nih.gov/pubmed/30970632
http://dx.doi.org/10.3390/biom9040143
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