{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T14:27:38Z","timestamp":1763389658416,"version":"build-2065373602"},"reference-count":40,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,11]],"date-time":"2022-11-11T00:00:00Z","timestamp":1668124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Technology and Science Foundation (FCT)","doi-asserted-by":"publisher","award":["PDE\/BDE\/114585\/2016","UIDB\/04295\/2020","UIDP\/04295\/2020"],"award-info":[{"award-number":["PDE\/BDE\/114585\/2016","UIDB\/04295\/2020","UIDP\/04295\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Foundation for Science and Technology to ISAMB","award":["PDE\/BDE\/114585\/2016","UIDB\/04295\/2020","UIDP\/04295\/2020"],"award-info":[{"award-number":["PDE\/BDE\/114585\/2016","UIDB\/04295\/2020","UIDP\/04295\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Chronic hepatitis C (CHC) progression is highly variable and can be influenced by lipid metabolism. The ATP-binding cassette transporter A1 (ABCA1) is involved in lipid metabolism and mediates cholesterol efflux from liver cells. ABCA1 gene polymorphism rs2230808 (R1587K) modulates lipid levels as it is located in an ABCA1 protein domain, which is essential for cholesterol efflux. We aimed to analyze the role of ABCA1 polymorphism R1587K (rs2230808) in modulating the biochemical parameters of lipid metabolism and liver function and its association with liver disease severity, according to gender. A total of 161 CHC patients were clinically, histologically, and biochemically evaluated. Genotyping was performed by melting-curve analysis and statistical analysis by SPSS 24.0. There were significant differences between ABCA1_rs2230808 genotypes and total cholesterol, \u03b3GT (\u03b3-glutamyl-transpeptidase), and HCV-RNA. Gender differences: in females, ABCA1_rs2230808 (GG or GA) was associated with higher HCV-RNA serum levels; in males, ABCA1_rs2230808 (GG or GA) was associated with higher \u03b3GT, lower total cholesterol, increased risk for \u03b3GT \u2265 38 UI\/L, and total cholesterol &lt; 4.92 mmol\/L. Only in the case of males were higher \u03b3GT and lower total cholesterol associated with severe fibrosis and steatosis. Total cholesterol &lt; 4.92 mmol\/L also associates with severe necroinflammation. We conclude that ABCA1_rs2230808 is gender-specific. ABCA1_rs2230808 Allele G was associated with different clinical and biochemical parameters, which are related to more severe liver disease.<\/jats:p>","DOI":"10.3390\/genes13112095","type":"journal-article","created":{"date-parts":[[2022,11,14]],"date-time":"2022-11-14T02:34:58Z","timestamp":1668393298000},"page":"2095","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["ABCA1 Polymorphism R1587K in Chronic Hepatitis C Is Gender-Specific and Modulates Liver Disease Severity through Its Influence on Cholesterol Metabolism and Liver Function: A Preliminary Study"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3527-3274","authenticated-orcid":false,"given":"Joana","family":"Ferreira","sequence":"first","affiliation":[{"name":"Institute for Scientific Research Bento Rocha Cabral, 1250-012 Lisbon, Portugal"},{"name":"Environmental Health Institute (ISAMB), Genetics Laboratory, Lisbon Medical School, University of Lisbon, 1649-004 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5773-5687","authenticated-orcid":false,"given":"Manuel","family":"Bicho","sequence":"additional","affiliation":[{"name":"Institute for Scientific Research Bento Rocha Cabral, 1250-012 Lisbon, Portugal"},{"name":"Environmental Health Institute (ISAMB), Genetics Laboratory, Lisbon Medical School, University of Lisbon, 1649-004 Lisbon, Portugal"}]},{"given":"F\u00e1tima","family":"Serejo","sequence":"additional","affiliation":[{"name":"Environmental Health Institute (ISAMB), Genetics Laboratory, Lisbon Medical School, University of Lisbon, 1649-004 Lisbon, Portugal"},{"name":"Gastroenterology and Hepatology Department, Hospital de Santa Maria, 1649-028 Lisbon, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"329","DOI":"10.7326\/0003-4819-158-5-201303050-00005","article-title":"Eradication of hepatitis C virus infection and the development of hepatocellular carcinoma: A meta-analysis of observational studies","volume":"158","author":"Morgan","year":"2013","journal-title":"Ann. Intern. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"564645","DOI":"10.1155\/2013\/564645","article-title":"Metabolic factors and chronic hepatitis C: A complex interplay","volume":"2013","author":"Macaluso","year":"2013","journal-title":"BioMed Res. Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1053\/j.gastro.2008.02.069","article-title":"Disease progression in chronic hepatitis C: Modifiable and nonmodifiable factors","volume":"134","author":"Missiha","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1111\/j.1365-3148.2008.00859.x","article-title":"Anti-hepatitis C virus-positive blood donors: Are women any different?","volume":"18","author":"Schiavon","year":"2008","journal-title":"Transfus. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1002\/hep.20463","article-title":"Progression of liver fibrosis in women infected with hepatitis C: Long-term benefit of estrogen exposure","volume":"40","author":"Martino","year":"2004","journal-title":"Hepatology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/S0168-8278(02)00299-4","article-title":"Steatosis accelerates fibrosis development over time in hepatitis C virus genotype 3 infected patients","volume":"37","author":"Westin","year":"2002","journal-title":"J. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1136\/gut.52.11.1638","article-title":"Liver fibrosis is not associated with steatosis but with necroinflammation in French patients with chronic hepatitis C","volume":"52","author":"Asselah","year":"2003","journal-title":"Gut"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1111\/jvh.12035","article-title":"Hepatitis C virus diversity and hepatic steatosis","volume":"20","author":"Roingeard","year":"2013","journal-title":"J. Viral Hepat."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s00281-012-0356-2","article-title":"Lipids and HCV","volume":"35","author":"Bassendine","year":"2013","journal-title":"Semin. Immunopathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/S0168-8278(01)00143-X","article-title":"Risk factors for diabetes mellitus and early insulin resistance in chronic hepatitis C","volume":"35","author":"Petit","year":"2001","journal-title":"J. Hepatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1111\/j.1365-2893.2005.00655.x","article-title":"Serum lipid pattern in chronic hepatitis C: Histological and virological correlations","volume":"13","author":"Siagris","year":"2006","journal-title":"J. Viral Hepat."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1111\/jgh.12313","article-title":"Chronic hepatitis C infection is associated with insulin resistance and lipid profiles","volume":"30","author":"Dai","year":"2015","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_13","first-page":"107","article-title":"Peroxisome proliferator-activated receptor-\u03b1 and-\u03b3 mRNA levels are reduced in chronic hepatitis C with steatosis and genotype 3 infection. Aliment","volume":"23","author":"Pazienza","year":"2006","journal-title":"Pharmacol. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"348","DOI":"10.5009\/gnl.2011.5.3.348","article-title":"Lipid profiles and hepatitis C viral markers in HCV-infected thalassemic patients","volume":"5","author":"Alavian","year":"2011","journal-title":"Gut Liver"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1002\/hep.23219","article-title":"Hepatitis C virus infection and its clearance alter circulating lipids: Implications for long-term follow-up","volume":"50","author":"Corey","year":"2009","journal-title":"Hepatology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/1476-511X-11-62","article-title":"Association of gender, ABCA1 gene polymorphisms and lipid profile in Greek young nurses","volume":"11","author":"Kolovou","year":"2012","journal-title":"Lipids Health Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1152\/physrev.00005.2005","article-title":"ATP-binding cassette transporter A1: A cell cholesterol exporter that protects against cardiovascular disease","volume":"85","author":"Oram","year":"2005","journal-title":"Physiol. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1161\/01.ATV.0000014804.35824.DA","article-title":"Increased atherosclerosis in hyperlipidemic mice with inactivation of ABCA1 in macrophages","volume":"22","author":"Aiello","year":"2002","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1016\/j.biochi.2010.04.002","article-title":"Suppression of ABCA1 by unsaturated fatty acids leads to lipid accumulation in HepG2 cells","volume":"92","author":"Yang","year":"2010","journal-title":"Biochimie"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1111\/jgh.12430","article-title":"ApoA-I and ABCA1 expression alleviates lipid accumulation in hepatocytes","volume":"29","author":"Liu","year":"2014","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"83","DOI":"10.2174\/1874192401408010083","article-title":"Impact of 3 Common ABCA1 Gene Polymorphisms on Optimal vs. Non-Optimal Lipid Profile in Greek Young Nurses","volume":"8","author":"Marvaki","year":"2014","journal-title":"Open Cardiovasc. Med. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.ijcard.2005.12.020","article-title":"A novel haplotype in ABCA1 gene affects plasma HDL-C concentration","volume":"31","author":"Saleheen","year":"2007","journal-title":"Int. J. Cardiol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Pasdar, A., Yadegarfar, G., Cumming, A., Whalley, L., St Clair, D., and MacLeod, M.J. (2007). The effect of ABCA1 gene polymorphisms on ischemic stroke and relationship with lipid profile. BMC Med. Genet., 8.","DOI":"10.1186\/1471-2350-8-30"},{"key":"ref_24","unstructured":"World Medical Association (, January June). World Medical Association (WMA) declaration of Helsinki\u2014Ethical principles for medical research involving human subjects. Proceedings of the 18th WMA General Assembly, Helsinki, Finland."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5444","DOI":"10.1093\/nar\/19.19.5444","article-title":"A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies","volume":"19","author":"Lahiri","year":"1991","journal-title":"Nucleic Acids Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/S0016-5085(19)35563-5","article-title":"One-second needle biopsy of the liver","volume":"35","author":"Menghini","year":"1958","journal-title":"Gastroenterology"},{"key":"ref_27","first-page":"1370","article-title":"Nonalcoholic steatohepatitis: A proposal for grading and staging the histological lesions","volume":"95","author":"Brunt","year":"2000","journal-title":"Am. J. Gastroenterol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1002\/hep.1840200104","article-title":"Intraobserver and Interobserver Variations in Liver Biopsy Interpretation in Patients with Chronic Hepatitis C","volume":"20","author":"Bedossa","year":"1994","journal-title":"Hepatology"},{"key":"ref_29","first-page":"8","article-title":"Transient hepatic elastography, a non-invasive method for assessing fibrosis in patients with chronic hepatitis C","volume":"14","author":"Serejo","year":"2007","journal-title":"GE J. Port. Gastroenterol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1111\/j.1365-2893.2011.01481.x","article-title":"Role of hepatitis C virus genotype 3 in liver fibrosis progression","volume":"18","author":"Probst","year":"2011","journal-title":"J. Viral Hepat."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"47","DOI":"10.7150\/ijms.3.47","article-title":"The natural history of hepatitis C virus (HCV) infection","volume":"3","author":"Chen","year":"2006","journal-title":"Int. J. Med. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3281","DOI":"10.3390\/v4123281","article-title":"Host genetic variants in the pathogenesis of hepatitis C","volume":"4","author":"Rau","year":"2012","journal-title":"Viruses"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1111\/j.1365-2893.2010.01394.x","article-title":"Serum lipids and their associations with viral levels and liver disease severity in a treatment-naive chronic hepatitis C type 1-infected cohort","volume":"18","author":"Ramcharran","year":"2011","journal-title":"J. Viral Hepat."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5404","DOI":"10.1128\/JVI.02529-09","article-title":"Gene expression profiling indicates the roles of host oxidative stress, apoptosis, lipid metabolism, and intracellular transport genes in the replication of hepatitis C virus","volume":"84","author":"Blackham","year":"2010","journal-title":"J. Virol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1002\/hep.26203","article-title":"Wright. Association of \u03b3-glutamyl transferase (GGT) activity with treatment and clinical outcomes in chronic hepatitis C (HCV)","volume":"57","author":"Everhart","year":"2013","journal-title":"Hepatology"},{"key":"ref_36","first-page":"387","article-title":"Correlation of Serum \u03b3 Glutamyl Transferase with Atherogenic Dyslipidemia in Obese Individuals","volume":"3","author":"Latha","year":"2015","journal-title":"Sch. J. App. Med. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1002\/hep.21239","article-title":"Impact of obesity on the treatment of chronic hepatitis C","volume":"43","author":"Charlton","year":"2006","journal-title":"Hepatology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"S68","DOI":"10.1016\/j.jhep.2014.08.003","article-title":"Facts and fictions of HCV and comorbidities: Steatosis, diabetes mellitus, and cardiovascular diseases","volume":"61","author":"Negro","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Bocchetta, S., Maillard, P., Yamamoto, M., Gondeau, C., Douam, F., Lebreton, S., Lagaye, S., Pol, S., Helle, F., and Plengpanich, W. (2014). Up-regulation of the ATP-binding cassette transporter A1 inhibits hepatitis C virus infection. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0092140"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"438","DOI":"10.2119\/molmed.2010.00004","article-title":"ATP-binding membrane Cassette Transporter A1 (ABCA1): A possible link between inflammation and reverse cholesterol transport","volume":"16","author":"Yin","year":"2010","journal-title":"Mol. Med."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/11\/2095\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:14:27Z","timestamp":1760145267000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/11\/2095"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,11]]},"references-count":40,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["genes13112095"],"URL":"https:\/\/doi.org\/10.3390\/genes13112095","relation":{},"ISSN":["2073-4425"],"issn-type":[{"type":"electronic","value":"2073-4425"}],"subject":[],"published":{"date-parts":[[2022,11,11]]}}}