Interferon-related genetic markers of necroinflammatory activity in chronic hepatitis C
Chronic hepatitis C (CHC) is a major cause of liver disease worldwide which often leads to progressive liver inflammation, fibrosis, cirrhosis and hepatocellular carcinoma (HCC). CHC displays heterogeneous progression depending on a broad set of factors, some of them intrinsic to each individual suc...
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| Veröffentlicht in: | PloS one 2017-07, Vol.12 (7), p.e0180927-e0180927 |
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| creator | López-Rodríguez, Rosario Hernández-Bartolomé, Ángel Borque, María Jesús Rodríguez-Muñoz, Yolanda Martín-Vílchez, Samuel García-Buey, Luisa González-Moreno, Leticia Real-Martínez, Yolanda Muñoz de Rueda, Paloma Salmerón, Javier Vidal-Castiñeira, José Ramón López-Larrea, Carlos Rodrigo, Luis Moreno-Otero, Ricardo Sanz-Cameno, Paloma |
| description | Chronic hepatitis C (CHC) is a major cause of liver disease worldwide which often leads to progressive liver inflammation, fibrosis, cirrhosis and hepatocellular carcinoma (HCC). CHC displays heterogeneous progression depending on a broad set of factors, some of them intrinsic to each individual such as the patient's genetic profile. This study aims to evaluate the contribution of certain genetic variants of crucial interferon alpha and lambda signaling pathways to the hepatic necroinflammatory activity (NIA) grade of CHC patients.
NIA was evaluated in 119 CHC patients by METAVIR scale and classified as low (NIA = 0-2, n = 80) or high grade (NIA = 3, n = 39). In a candidate gene approach, 64 SNPs located in 30 different genes related to interferon pathways (IL-28B, IFNAR1-2, JAK-STAT and OAS1-3, among others) were genotyped using the Illumina GoldenGate® Genotyping Assay. Statistical association was determined by logistic regression and expressed as OR and 95% CI. Those SNPs significantly associated were further adjusted by other covariates.
Seven SNPs located in IL-28B (rs12979860), JAK1 (rs11576173 and rs1497056), TYK2 (rs280519), OAS1 (rs2057778), SOCS1 (rs33932899) and RNASEL (rs3738579) genes were significantly related to severe NIA grade (p40 IU/L (p40 IU/L), TYK2 rs280519 (G allele) and RNASEL rs3738579 (G allele) were factors independently associated with elevated NIA (p |
| doi_str_mv | 10.1371/journal.pone.0180927 |
| format | Article |
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NIA was evaluated in 119 CHC patients by METAVIR scale and classified as low (NIA = 0-2, n = 80) or high grade (NIA = 3, n = 39). In a candidate gene approach, 64 SNPs located in 30 different genes related to interferon pathways (IL-28B, IFNAR1-2, JAK-STAT and OAS1-3, among others) were genotyped using the Illumina GoldenGate® Genotyping Assay. Statistical association was determined by logistic regression and expressed as OR and 95% CI. Those SNPs significantly associated were further adjusted by other covariates.
Seven SNPs located in IL-28B (rs12979860), JAK1 (rs11576173 and rs1497056), TYK2 (rs280519), OAS1 (rs2057778), SOCS1 (rs33932899) and RNASEL (rs3738579) genes were significantly related to severe NIA grade (p<0.05). Regarding to clinical variables, elevated NIA was notably associated with aspartate aminotransferase (AST) serum levels >40 IU/L (p<0.05) but not with other clinical factors. Multivariate logistic regression analysis of these factors reflected that AST (>40 IU/L), TYK2 rs280519 (G allele) and RNASEL rs3738579 (G allele) were factors independently associated with elevated NIA (p<0.05). AST concentration showed a moderate AUC value (AUC = 0.63), similar to TYK2 (rs280519) and RNASEL (rs3738579) SNPs (AUC = 0.61, both) in the ROC_AUC analysis. Interestingly, the model including all significant variables reached a considerable predictive value (AUC = 0.74).
The identified genetic variants in interferon signaling pathways may constitute useful prognostic markers of CHC progression. Further validation in larger cohorts of patients is needed.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0180927</identifier><identifier>PMID: 28704535</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>2',5'-Oligoadenylate Synthetase - genetics ; Adult ; Aged ; Alleles ; Aspartate Aminotransferases - blood ; Assaying ; Biology and Life Sciences ; Cirrhosis ; Dosage and administration ; Endoribonucleases - genetics ; Female ; Fibrosis ; Gastroenterology ; Gene expression ; Genes ; Genetic aspects ; Genetic markers ; Genomes ; Genotyping ; Hepatitis ; Hepatitis C ; Hepatitis C virus ; Hepatitis C, Chronic - blood ; Hepatitis C, Chronic - genetics ; Hepatitis C, Chronic - pathology ; Hepatocellular carcinoma ; Humans ; Infections ; Inflammation ; Interferon ; Interferons ; Interleukins - genetics ; Janus kinase ; Janus Kinase 1 - genetics ; Laboratories ; Liver ; Liver cancer ; Liver cirrhosis ; Liver diseases ; Male ; Markers ; Medicine and Health Sciences ; Middle Aged ; Pathways ; Patients ; Polymorphism, Single Nucleotide ; Prognosis ; Proteins ; Quality ; Regression analysis ; Serum levels ; Signal transduction ; Single-nucleotide polymorphism ; Suppressor of Cytokine Signaling 1 Protein - genetics ; TYK2 Kinase - genetics ; Tyk2 protein ; Virology ; Viruses ; α-Interferon</subject><ispartof>PloS one, 2017-07, Vol.12 (7), p.e0180927-e0180927</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 López-Rodríguez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2017 López-Rodríguez et al 2017 López-Rodríguez et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-45acf6e8966ce7b23a39b2349159165f2b02f96ec625487ae2e49b11263a93cd3</citedby><cites>FETCH-LOGICAL-c692t-45acf6e8966ce7b23a39b2349159165f2b02f96ec625487ae2e49b11263a93cd3</cites><orcidid>0000-0001-5308-2167</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5507534/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5507534/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,729,782,786,866,887,2104,2930,23873,27931,27932,53798,53800</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28704535$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Avila, Matias A.</contributor><creatorcontrib>López-Rodríguez, Rosario</creatorcontrib><creatorcontrib>Hernández-Bartolomé, Ángel</creatorcontrib><creatorcontrib>Borque, María Jesús</creatorcontrib><creatorcontrib>Rodríguez-Muñoz, Yolanda</creatorcontrib><creatorcontrib>Martín-Vílchez, Samuel</creatorcontrib><creatorcontrib>García-Buey, Luisa</creatorcontrib><creatorcontrib>González-Moreno, Leticia</creatorcontrib><creatorcontrib>Real-Martínez, Yolanda</creatorcontrib><creatorcontrib>Muñoz de Rueda, Paloma</creatorcontrib><creatorcontrib>Salmerón, Javier</creatorcontrib><creatorcontrib>Vidal-Castiñeira, José Ramón</creatorcontrib><creatorcontrib>López-Larrea, Carlos</creatorcontrib><creatorcontrib>Rodrigo, Luis</creatorcontrib><creatorcontrib>Moreno-Otero, Ricardo</creatorcontrib><creatorcontrib>Sanz-Cameno, Paloma</creatorcontrib><title>Interferon-related genetic markers of necroinflammatory activity in chronic hepatitis C</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Chronic hepatitis C (CHC) is a major cause of liver disease worldwide which often leads to progressive liver inflammation, fibrosis, cirrhosis and hepatocellular carcinoma (HCC). CHC displays heterogeneous progression depending on a broad set of factors, some of them intrinsic to each individual such as the patient's genetic profile. This study aims to evaluate the contribution of certain genetic variants of crucial interferon alpha and lambda signaling pathways to the hepatic necroinflammatory activity (NIA) grade of CHC patients.
NIA was evaluated in 119 CHC patients by METAVIR scale and classified as low (NIA = 0-2, n = 80) or high grade (NIA = 3, n = 39). In a candidate gene approach, 64 SNPs located in 30 different genes related to interferon pathways (IL-28B, IFNAR1-2, JAK-STAT and OAS1-3, among others) were genotyped using the Illumina GoldenGate® Genotyping Assay. Statistical association was determined by logistic regression and expressed as OR and 95% CI. Those SNPs significantly associated were further adjusted by other covariates.
Seven SNPs located in IL-28B (rs12979860), JAK1 (rs11576173 and rs1497056), TYK2 (rs280519), OAS1 (rs2057778), SOCS1 (rs33932899) and RNASEL (rs3738579) genes were significantly related to severe NIA grade (p<0.05). Regarding to clinical variables, elevated NIA was notably associated with aspartate aminotransferase (AST) serum levels >40 IU/L (p<0.05) but not with other clinical factors. Multivariate logistic regression analysis of these factors reflected that AST (>40 IU/L), TYK2 rs280519 (G allele) and RNASEL rs3738579 (G allele) were factors independently associated with elevated NIA (p<0.05). AST concentration showed a moderate AUC value (AUC = 0.63), similar to TYK2 (rs280519) and RNASEL (rs3738579) SNPs (AUC = 0.61, both) in the ROC_AUC analysis. Interestingly, the model including all significant variables reached a considerable predictive value (AUC = 0.74).
The identified genetic variants in interferon signaling pathways may constitute useful prognostic markers of CHC progression. Further validation in larger cohorts of patients is needed.</description><subject>2',5'-Oligoadenylate Synthetase - genetics</subject><subject>Adult</subject><subject>Aged</subject><subject>Alleles</subject><subject>Aspartate Aminotransferases - blood</subject><subject>Assaying</subject><subject>Biology and Life Sciences</subject><subject>Cirrhosis</subject><subject>Dosage and administration</subject><subject>Endoribonucleases - genetics</subject><subject>Female</subject><subject>Fibrosis</subject><subject>Gastroenterology</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic markers</subject><subject>Genomes</subject><subject>Genotyping</subject><subject>Hepatitis</subject><subject>Hepatitis C</subject><subject>Hepatitis C virus</subject><subject>Hepatitis C, Chronic - blood</subject><subject>Hepatitis C, Chronic - genetics</subject><subject>Hepatitis C, Chronic - pathology</subject><subject>Hepatocellular carcinoma</subject><subject>Humans</subject><subject>Infections</subject><subject>Inflammation</subject><subject>Interferon</subject><subject>Interferons</subject><subject>Interleukins - genetics</subject><subject>Janus kinase</subject><subject>Janus Kinase 1 - genetics</subject><subject>Laboratories</subject><subject>Liver</subject><subject>Liver cancer</subject><subject>Liver cirrhosis</subject><subject>Liver diseases</subject><subject>Male</subject><subject>Markers</subject><subject>Medicine and Health Sciences</subject><subject>Middle Aged</subject><subject>Pathways</subject><subject>Patients</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Prognosis</subject><subject>Proteins</subject><subject>Quality</subject><subject>Regression analysis</subject><subject>Serum levels</subject><subject>Signal transduction</subject><subject>Single-nucleotide polymorphism</subject><subject>Suppressor of Cytokine Signaling 1 Protein - genetics</subject><subject>TYK2 Kinase - genetics</subject><subject>Tyk2 protein</subject><subject>Virology</subject><subject>Viruses</subject><subject>α-Interferon</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl1r2zAYhc3YWLtu_2BshsHYLpLp29bNoIR9BAqFfV4KWX6dqHOkVJLL8u-nLG6JRy-GwTbyc458Xp2ieI7RHNMKv7vyQ3C6n2-9gznCNZKkelCcYknJTBBEHx69nxRPYrxCiNNaiMfFCakrxDjlp8XPpUsQOgjezQL0OkFbrsBBsqbc6PALQix9VzowwVvX9Xqz0cmHXalNsjc27UrrSrPO8ixYw1Ynm2wsF0-LR53uIzwbn2fF948fvi0-zy4uPy0X5xczIyRJM8a16QTUUggDVUOopjLfmcRcYsE70iDSSQFGEM7qSgMBJhuMiaBaUtPSs-LlwXfb-6jGmUSFJZac5LQyE8sD0Xp9pbbB5lg75bVVfxd8WCkdctweFNQGGS6atu0IY7hrsNTAqqaWpsJG773ej7sNzQZaAy4F3U9Mp1-cXauVv1Gco4pTlg3ejAbBXw8Qk9rYaKDvtQM_7P-b0IohjOuMvvoHvT_dSK10DpBPyOd9zd5UnTNZU4EJ4Zma30Plq4WNNblAnc3rE8HbiSAzCX6nlR5iVMuvX_6fvfwxZV8fsWvQfVpH3w_JehenIDuAuXcxBujuhoyR2vf_dhpq33819j_LXhwf0J3otvD0D69QAIY</recordid><startdate>20170712</startdate><enddate>20170712</enddate><creator>López-Rodríguez, 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genetic markers of necroinflammatory activity in chronic hepatitis C</title><author>López-Rodríguez, Rosario ; Hernández-Bartolomé, Ángel ; Borque, María Jesús ; Rodríguez-Muñoz, Yolanda ; Martín-Vílchez, Samuel ; García-Buey, Luisa ; González-Moreno, Leticia ; Real-Martínez, Yolanda ; Muñoz de Rueda, Paloma ; Salmerón, Javier ; Vidal-Castiñeira, José Ramón ; López-Larrea, Carlos ; Rodrigo, Luis ; Moreno-Otero, Ricardo ; Sanz-Cameno, Paloma</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-45acf6e8966ce7b23a39b2349159165f2b02f96ec625487ae2e49b11263a93cd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>2',5'-Oligoadenylate Synthetase - genetics</topic><topic>Adult</topic><topic>Aged</topic><topic>Alleles</topic><topic>Aspartate Aminotransferases - blood</topic><topic>Assaying</topic><topic>Biology and Life Sciences</topic><topic>Cirrhosis</topic><topic>Dosage and 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Sciences</topic><topic>Middle Aged</topic><topic>Pathways</topic><topic>Patients</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Prognosis</topic><topic>Proteins</topic><topic>Quality</topic><topic>Regression analysis</topic><topic>Serum levels</topic><topic>Signal transduction</topic><topic>Single-nucleotide polymorphism</topic><topic>Suppressor of Cytokine Signaling 1 Protein - genetics</topic><topic>TYK2 Kinase - genetics</topic><topic>Tyk2 protein</topic><topic>Virology</topic><topic>Viruses</topic><topic>α-Interferon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>López-Rodríguez, Rosario</creatorcontrib><creatorcontrib>Hernández-Bartolomé, Ángel</creatorcontrib><creatorcontrib>Borque, María Jesús</creatorcontrib><creatorcontrib>Rodríguez-Muñoz, Yolanda</creatorcontrib><creatorcontrib>Martín-Vílchez, Samuel</creatorcontrib><creatorcontrib>García-Buey, Luisa</creatorcontrib><creatorcontrib>González-Moreno, 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Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>López-Rodríguez, Rosario</au><au>Hernández-Bartolomé, Ángel</au><au>Borque, María Jesús</au><au>Rodríguez-Muñoz, Yolanda</au><au>Martín-Vílchez, Samuel</au><au>García-Buey, Luisa</au><au>González-Moreno, Leticia</au><au>Real-Martínez, Yolanda</au><au>Muñoz de Rueda, Paloma</au><au>Salmerón, Javier</au><au>Vidal-Castiñeira, José Ramón</au><au>López-Larrea, Carlos</au><au>Rodrigo, Luis</au><au>Moreno-Otero, Ricardo</au><au>Sanz-Cameno, Paloma</au><au>Avila, Matias A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interferon-related genetic markers of necroinflammatory activity in chronic hepatitis C</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2017-07-12</date><risdate>2017</risdate><volume>12</volume><issue>7</issue><spage>e0180927</spage><epage>e0180927</epage><pages>e0180927-e0180927</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Chronic hepatitis C (CHC) is a major cause of liver disease worldwide which often leads to progressive liver inflammation, fibrosis, cirrhosis and hepatocellular carcinoma (HCC). CHC displays heterogeneous progression depending on a broad set of factors, some of them intrinsic to each individual such as the patient's genetic profile. This study aims to evaluate the contribution of certain genetic variants of crucial interferon alpha and lambda signaling pathways to the hepatic necroinflammatory activity (NIA) grade of CHC patients.
NIA was evaluated in 119 CHC patients by METAVIR scale and classified as low (NIA = 0-2, n = 80) or high grade (NIA = 3, n = 39). In a candidate gene approach, 64 SNPs located in 30 different genes related to interferon pathways (IL-28B, IFNAR1-2, JAK-STAT and OAS1-3, among others) were genotyped using the Illumina GoldenGate® Genotyping Assay. Statistical association was determined by logistic regression and expressed as OR and 95% CI. Those SNPs significantly associated were further adjusted by other covariates.
Seven SNPs located in IL-28B (rs12979860), JAK1 (rs11576173 and rs1497056), TYK2 (rs280519), OAS1 (rs2057778), SOCS1 (rs33932899) and RNASEL (rs3738579) genes were significantly related to severe NIA grade (p<0.05). Regarding to clinical variables, elevated NIA was notably associated with aspartate aminotransferase (AST) serum levels >40 IU/L (p<0.05) but not with other clinical factors. Multivariate logistic regression analysis of these factors reflected that AST (>40 IU/L), TYK2 rs280519 (G allele) and RNASEL rs3738579 (G allele) were factors independently associated with elevated NIA (p<0.05). AST concentration showed a moderate AUC value (AUC = 0.63), similar to TYK2 (rs280519) and RNASEL (rs3738579) SNPs (AUC = 0.61, both) in the ROC_AUC analysis. Interestingly, the model including all significant variables reached a considerable predictive value (AUC = 0.74).
The identified genetic variants in interferon signaling pathways may constitute useful prognostic markers of CHC progression. Further validation in larger cohorts of patients is needed.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28704535</pmid><doi>10.1371/journal.pone.0180927</doi><tpages>e0180927</tpages><orcidid>https://orcid.org/0000-0001-5308-2167</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2017-07, Vol.12 (7), p.e0180927-e0180927 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1919523869 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS) Journals Open Access; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 2',5'-Oligoadenylate Synthetase - genetics Adult Aged Alleles Aspartate Aminotransferases - blood Assaying Biology and Life Sciences Cirrhosis Dosage and administration Endoribonucleases - genetics Female Fibrosis Gastroenterology Gene expression Genes Genetic aspects Genetic markers Genomes Genotyping Hepatitis Hepatitis C Hepatitis C virus Hepatitis C, Chronic - blood Hepatitis C, Chronic - genetics Hepatitis C, Chronic - pathology Hepatocellular carcinoma Humans Infections Inflammation Interferon Interferons Interleukins - genetics Janus kinase Janus Kinase 1 - genetics Laboratories Liver Liver cancer Liver cirrhosis Liver diseases Male Markers Medicine and Health Sciences Middle Aged Pathways Patients Polymorphism, Single Nucleotide Prognosis Proteins Quality Regression analysis Serum levels Signal transduction Single-nucleotide polymorphism Suppressor of Cytokine Signaling 1 Protein - genetics TYK2 Kinase - genetics Tyk2 protein Virology Viruses α-Interferon |
| title | Interferon-related genetic markers of necroinflammatory activity in chronic hepatitis C |
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