{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T15:32:22Z","timestamp":1784302342575,"version":"3.55.0"},"reference-count":48,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2019,4,9]],"date-time":"2019-04-09T00:00:00Z","timestamp":1554768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI17CIII\/00003"],"award-info":[{"award-number":["PI17CIII\/00003"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>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 &lt; 0.001), while LSM values and the percentage of patients with cirrhosis increased (p &lt; 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 \u2265 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 \u2265 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.<\/jats:p>","DOI":"10.3390\/biom9040143","type":"journal-article","created":{"date-parts":[[2019,4,10]],"date-time":"2019-04-10T03:47:36Z","timestamp":1554868056000},"page":"143","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Impact of DARC rs12075 Variants on Liver Fibrosis Progression in Patients with Chronic Hepatitis C: A Retrospective Study"],"prefix":"10.3390","volume":"9","author":[{"given":"Mar\u00eda \u00c1ngeles","family":"Jim\u00e9nez-Sousa","sequence":"first","affiliation":[{"name":"Unidad de Infecci\u00f3n Viral e Inmunidad, Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, 28220 Majadahonda, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Zaida","family":"G\u00f3mez-Moreno","sequence":"additional","affiliation":[{"name":"Servicio de Digestivo, Hospital Virgen de la Salud, 45004 Toledo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Pineda-Tenor","sequence":"additional","affiliation":[{"name":"Servicio de Laboratorio Cl\u00ednico, Hospital de Antequera, 29200 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Jos\u00e9","family":"S\u00e1nchez-Ruano","sequence":"additional","affiliation":[{"name":"Servicio de Digestivo, Hospital Virgen de la Salud, 45004 Toledo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Artaza-Varasa","sequence":"additional","affiliation":[{"name":"Servicio de Digestivo, Hospital Virgen de la Salud, 45004 Toledo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Martin-Vicente","sequence":"additional","affiliation":[{"name":"Unidad de Infecci\u00f3n Viral e Inmunidad, Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, 28220 Majadahonda, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5110-2213","authenticated-orcid":false,"given":"Amanda","family":"Fern\u00e1ndez-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Unidad de Infecci\u00f3n Viral e Inmunidad, Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, 28220 Majadahonda, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isidoro","family":"Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Unidad de Infecci\u00f3n Viral e Inmunidad, Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, 28220 Majadahonda, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8783-0450","authenticated-orcid":false,"given":"Salvador","family":"Resino","sequence":"additional","affiliation":[{"name":"Unidad de Infecci\u00f3n Viral e Inmunidad, Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, 28220 Majadahonda, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,4,9]]},"reference":[{"key":"ref_1","unstructured":"WHO (2017). Global Hepatitis Report, World Health Organization."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1034\/j.1600-0676.2002.01623.x","article-title":"Progression of fibrosis in untreated patients with hepatitis C virus infection","volume":"22","author":"Lagging","year":"2002","journal-title":"Liver"},{"key":"ref_3","first-page":"S21","article-title":"Course and outcome of hepatitis C","volume":"36","author":"Hoofnagle","year":"2002","journal-title":"Hepatology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.jhep.2016.06.015","article-title":"Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct-acting antivirals","volume":"65","author":"Conti","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1016\/S0140-6736(18)30010-2","article-title":"Hepatocellular carcinoma","volume":"391","author":"Forner","year":"2018","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1136\/gutjnl-2014-306997","article-title":"Impact of common risk factors of fibrosis progression in chronic hepatitis C","volume":"64","author":"Rueger","year":"2015","journal-title":"Gut"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S22","DOI":"10.1016\/j.jhep.2016.07.037","article-title":"Host\u2014Hepatitis C viral interactions: The role of genetics","volume":"65","author":"Heim","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.jhep.2015.03.025","article-title":"EASL recommendations on treatment of hepatitis C 2015","volume":"63","author":"Pawlotsky","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1111\/cpf.12297","article-title":"Contemporary use of elastography in liver fibrosis and portal hypertension","volume":"37","author":"Thiele","year":"2017","journal-title":"Clin. Physiol. Funct. Imaging"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1016\/S0140-6736(14)60121-5","article-title":"Liver cirrhosis","volume":"383","author":"Tsochatzis","year":"2014","journal-title":"Lancet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1097\/QCO.0b013e32835635df","article-title":"Coinfection by human immunodeficiency virus and hepatitis C virus: Noninvasive assessment and staging of fibrosis","volume":"25","author":"Resino","year":"2012","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1159\/000374097","article-title":"Noninvasive assessment of liver fibrosis","volume":"33","author":"Castera","year":"2015","journal-title":"Dig. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1086\/646614","article-title":"Peripheral CXCR3-associated chemokines as biomarkers of fibrosis in chronic hepatitis C virus infection","volume":"200","author":"Zeremski","year":"2009","journal-title":"J. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"786","DOI":"10.2174\/1389450116666150804105937","article-title":"Chemokines in the pathogenesis and as therapeutical markers and targets of HCV chronic infection and HCV extrahepatic manifestations","volume":"18","author":"Fallahi","year":"2017","journal-title":"Curr. Drug Targets"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1053\/gast.2003.50061","article-title":"Associations of chemokine system polymorphisms with clinical outcomes and treatment responses of chronic hepatitis C","volume":"124","author":"Promrat","year":"2003","journal-title":"Gastroenterology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1016\/j.hep.2003.09.027","article-title":"Association of genetic variants of the chemokine receptor CCR5 and its ligands, rantes and MCP-2, with outcome of HCV infection","volume":"38","author":"Hellier","year":"2003","journal-title":"Hepatology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/S1471-4906(01)01941-X","article-title":"Decoy receptors: A strategy to regulate inflammatory cytokines and chemokines","volume":"22","author":"Mantovani","year":"2001","journal-title":"Trends Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"387","DOI":"10.3109\/10408367509107049","article-title":"Present status of the duffy blood group system","volume":"5","author":"Marsh","year":"1975","journal-title":"CRC Crit. Rev. Clin. Lab. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.bbrc.2004.06.146","article-title":"The human duffy antigen binds selected inflammatory but not homeostatic chemokines","volume":"321","author":"Gardner","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1182\/blood.V89.2.701","article-title":"Detection of Duffy antigen in the plasma membranes and caveolae of vascular endothelial and epithelial cells of nonerythroid organs","volume":"89","author":"Chaudhuri","year":"1997","journal-title":"Blood"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/ni.1675","article-title":"The Duffy antigen receptor for chemokines transports chemokines and supports their promigratory activity","volume":"10","author":"Pruenster","year":"2009","journal-title":"Nat. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5244","DOI":"10.4049\/jimmunol.170.10.5244","article-title":"Duffy antigen facilitates movement of chemokine across the endothelium in vitro and promotes neutrophil transmigration in vitro and in vivo","volume":"170","author":"Lee","year":"2003","journal-title":"J. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1172\/JCI115442","article-title":"Red blood cells are a sink for interleukin 8, a leukocyte chemotaxin","volume":"88","author":"Darbonne","year":"1991","journal-title":"J. Clin. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"717","DOI":"10.7754\/Clin.Lab.2016.161027","article-title":"Intracellular storage of duffy antigen-binding chemokines by duffy-positive red blood cells","volume":"63","author":"Yamamoto","year":"2017","journal-title":"Clin. Lab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S0006-291X(03)00293-6","article-title":"A role of the duffy antigen for the maintenance of plasma chemokine concentrations","volume":"303","author":"Fukuma","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5289","DOI":"10.1182\/blood-2009-05-221382","article-title":"Duffy antigen receptor for chemokines (DARC) polymorphism regulates circulating concentrations of monocyte chemoattractant protein-1 and other inflammatory mediators","volume":"115","author":"Schnabel","year":"2010","journal-title":"Blood"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1053\/j.gastro.2014.06.043","article-title":"Roles for chemokines in liver disease","volume":"147","author":"Marra","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Jimenez-Sousa, M.A., Gomez-Moreno, A.Z., Pineda-Tenor, D., Medrano, L.M., Sanchez-Ruano, J.J., Fernandez-Rodriguez, A., Artaza-Varasa, T., Saura-Montalban, J., Vazquez-Moron, S., and Ryan, P. (2018). The IL7RA rs6897932 polymorphism is associated with progression of liver fibrosis in patients with chronic hepatitis C: Repeated measurements design. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0197115"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/j.1478-3231.2011.02703.x","article-title":"2011 european association of the study of the liver hepatitis C virus clinical practice guidelines","volume":"32","author":"Calvaruso","year":"2012","journal-title":"Liver Int."},{"key":"ref_30","unstructured":"European Association for Study of Liver (2014). EASL clinical practice guidelines: Management of hepatitis C virus infection. J. Hepatol."},{"key":"ref_31","first-page":"2","article-title":"SNP genotyping using the sequenom MassARRAY iPLEX platform","volume":"Volume 60","author":"Haines","year":"2009","journal-title":"Current Protocols in Human Genetics"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.jcv.2018.04.008","article-title":"PNPLA3 rs738409 polymorphism is associated with liver fibrosis progression in patients with chronic hepatitis C: A repeated measures study","volume":"103","author":"Resino","year":"2018","journal-title":"J. Clin. Virol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Jimenez-Sousa, M.A., Gomez-Moreno, A.Z., Pineda-Tenor, D., Brochado-Kith, O., Sanchez-Ruano, J.J., Artaza-Varasa, T., Gomez-Sanz, A., Fernandez-Rodriguez, A., and Resino, S. (2018). The myeloid-epithelial-reproductive tyrosine kinase (MERKT) rs4374383 polymorphism predicts progression of liver fibrosis in hepatitis C virus-infected patients: A longitudinal study. J. Clin. Med., 7.","DOI":"10.20944\/preprints201810.0448.v1"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1053\/j.gastro.2004.11.018","article-title":"Prospective comparison of transient elastography, fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C","volume":"128","author":"Castera","year":"2005","journal-title":"Gastroenterology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1002\/(SICI)1097-0258(19990715)18:13<1707::AID-SIM138>3.0.CO;2-H","article-title":"Longitudinal data analysis (repeated measures) in clinical trials","volume":"18","author":"Albert","year":"1999","journal-title":"Stat. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1002\/(SICI)1097-0258(20000330)19:6<861::AID-SIM407>3.0.CO;2-F","article-title":"Repeated measures in clinical trials: Simple strategies for analysis using summary measures","volume":"19","author":"Senn","year":"2000","journal-title":"Stat. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1182\/blood-2008-07-166264","article-title":"Loss of red cell chemokine scavenging promotes transfusion-related lung inflammation","volume":"113","author":"Mangalmurti","year":"2009","journal-title":"Blood"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1097\/01.TP.0000061228.38243.26","article-title":"The influence of duffy blood group on renal allograft outcome in African Americans","volume":"75","author":"Akalin","year":"2003","journal-title":"Transplantation"},{"key":"ref_39","first-page":"185","article-title":"Human duffy blood group alloantigen system influences the measurement of monocyte chemoattractant protein-1 (MCP-1) in serum but not in plasma","volume":"58","author":"Aragones","year":"2012","journal-title":"Clin. Lab."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Naitza, S., Porcu, E., Steri, M., Taub, D.D., Mulas, A., Xiao, X., Strait, J., Dei, M., Lai, S., and Busonero, F. (2012). A genome-wide association scan on the levels of markers of inflammation in Sardinians reveals associations that underpin its complex regulation. PLoS Genet., 8.","DOI":"10.1371\/journal.pgen.1002480"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.cyto.2014.12.019","article-title":"Duffy antigen receptor genetic variant and the association with interleukin 8 levels","volume":"72","author":"Kumar","year":"2015","journal-title":"Cytokine"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1177\/1358863X14554034","article-title":"Understanding the role of circulating chemokine (C-C motif) ligand 2 in patients with chronic ischemia threatening the lower extremities","volume":"19","author":"Rull","year":"2014","journal-title":"Vasc. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.cyto.2012.08.029","article-title":"Genome-wide association replicates the association of duffy antigen receptor for chemokines (DARC) polymorphisms with serum monocyte chemoattractant protein-1 (MCP-1) levels in Hispanic children","volume":"60","author":"Voruganti","year":"2012","journal-title":"Cytokine"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1007\/s00439-011-1103-9","article-title":"Genetic variants associated with the white blood cell count in 13,923 subjects in the emerge network","volume":"131","author":"Crosslin","year":"2012","journal-title":"Hum. Genet."},{"key":"ref_45","first-page":"423","article-title":"Increased expression of monocyte chemotactic protein-1 during active hepatic fibrogenesis: Correlation with monocyte infiltration","volume":"152","author":"Marra","year":"1998","journal-title":"Am. J. Pathol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4427","DOI":"10.3748\/wjg.v22.i18.4427","article-title":"Thrombin activation and liver inflammation in advanced hepatitis C virus infection","volume":"22","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.humimm.2010.12.002","article-title":"A duffy antigen receptor for chemokines (DARC) polymorphism that determines pro-fibrotic chemokine serum concentrations is not directly associated with severity of hepatitis C infection","volume":"72","author":"Lettow","year":"2011","journal-title":"Hum. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.cmi.2016.09.017","article-title":"Role of assessing liver fibrosis in management of chronic hepatitis C virus infection","volume":"22","author":"Carmona","year":"2016","journal-title":"Clin. Microbiol. Infect."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/9\/4\/143\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:44:01Z","timestamp":1760186641000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/9\/4\/143"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,9]]},"references-count":48,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2019,4]]}},"alternative-id":["biom9040143"],"URL":"https:\/\/doi.org\/10.3390\/biom9040143","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,9]]}}}