{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T17:33:30Z","timestamp":1769016810316,"version":"3.49.0"},"reference-count":32,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T00:00:00Z","timestamp":1647216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>There is growing evidence that gallstone formation may be genetically determined. Recent studies have shown that polymorphism of genes encoding proteins involved in bile acid transport may be associated with the risk of gallstone disease. The aim of this study was to investigate the association between SLCO1B3 (rs4149117:G&gt;T, rs7311358:A&gt;G) and ABCC3 (rs4793665:T&gt;C, rs11568591:G&gt;A) genetic variants and susceptibility to cholesterol gallstone disease, as well as gallstone composition. The study included 317 patients suffering from cholelithiasis who underwent cholecystostomy and 249 controls with no evidence of stones, confirmed by ultrasound examination. There were no statistically significant differences in the distribution of studied gene polymorphisms between patients with gallstone disease and healthy controls. No significant associations were observed between studied genotypes and the content of analyzed gallstone components: total cholesterol, bilirubin, CaCO3, nor the total bile acids. There was also no association between bile acid content in gallstones and the polymorphisms studied. The results of this study suggest that polymorphisms of SLCO1B3 and ABCC3 genes are not a valuable marker of gallstone disease susceptibility and do not influence gallstone composition.<\/jats:p>","DOI":"10.3390\/genes13030512","type":"journal-article","created":{"date-parts":[[2022,3,15]],"date-time":"2022-03-15T03:06:10Z","timestamp":1647313570000},"page":"512","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Association Study of SLCO1B3 and ABCC3 Genetic Variants in Gallstone Disease"],"prefix":"10.3390","volume":"13","author":[{"given":"Boles\u0142aw","family":"Banach","sequence":"first","affiliation":[{"name":"Department of Physiology, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrzej","family":"Modrzejewski","sequence":"additional","affiliation":[{"name":"Clinical Department of General Surgery, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zygmunt","family":"Juzyszyn","sequence":"additional","affiliation":[{"name":"Department of Physiology, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mateusz","family":"Kurzawski","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomasz","family":"Sroczynski","sequence":"additional","affiliation":[{"name":"Department of Physiology, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6557-1208","authenticated-orcid":false,"given":"Andrzej","family":"Pawlik","sequence":"additional","affiliation":[{"name":"Department of Physiology, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1097\/MOG.0000000000000418","article-title":"Incidence of gallstone disease and complications","volume":"34","author":"Shabanzadeh","year":"2018","journal-title":"Curr. Opin. Gastroenterol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/ncpgasthep0257","article-title":"Mechanisms of disease: The genetic epidemiology of gallbladder stones","volume":"2","author":"Lammert","year":"2005","journal-title":"Nat. Clin. Pract. Gastroenterol. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1002\/hep.20654","article-title":"Genetic and environmental influences on symptomatic gallstone disease: A Swedish study of 43,141 twin pairs","volume":"41","author":"Katsika","year":"2005","journal-title":"Hepatology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/S0016-5085(03)00898-9","article-title":"ABCB4 gene mutation\u2014Associated cholelithiasis in adults","volume":"125","author":"Rosmorduc","year":"2003","journal-title":"Gastroenterology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1053\/j.gastro.2004.04.065","article-title":"Benign recurrent intrahepatic cholestasis type 2 is caused by mutations in ABCB11","volume":"127","author":"Sturm","year":"2004","journal-title":"Gastroenterology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1038\/ng2101","article-title":"A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease","volume":"39","author":"Buch","year":"2007","journal-title":"Nat. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1007\/s11894-004-0042-1","article-title":"Genetic analysis of cholesterol gallstone formation: Searching for Lith (gallstone) genes","volume":"6","author":"Wang","year":"2004","journal-title":"Curr. Gastroenterol. Rep."},{"key":"ref_8","first-page":"G1285","article-title":"Molecular aspects of hepatobiliary transport","volume":"272","author":"Muller","year":"1997","journal-title":"Am. J. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.bbamcr.2006.04.014","article-title":"Principles of hepatic organic anion transporter regulation during cholestasis, inflammation and liver regeneration","volume":"1773","author":"Geier","year":"2007","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1053\/jhep.2001.26213","article-title":"Up-regulation of basolateral multidrug resistance protein 3 (Mrp3) in cholestatic rat liver","volume":"34","author":"Donner","year":"2001","journal-title":"Hepatology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.jhep.2003.12.001","article-title":"Multidrug resistance-associated protein 4 is up-regulated in liver but down-regulated in kidney in obstructive cholestasis in the rat","volume":"40","author":"Denk","year":"2004","journal-title":"J. Hepatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1517\/17425255.4.1.51","article-title":"The functional consequences of genetic variations in transporter genes encoding human organic anion-transporting polypeptide family members","volume":"4","author":"Seithel","year":"2008","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1097\/01.fpc.0000114744.08559.92","article-title":"Mutations in the SLCO1B3 gene affecting the substrate specificity of the hepatocellular uptake transporter OATP1B3 (OATP8)","volume":"14","author":"Letschert","year":"2004","journal-title":"Pharmacogenetics"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"406","DOI":"10.2133\/dmpk.23.406","article-title":"Influence of SLCO1B3 Gene Polymorphism on the Pharmacokinetics of Digoxin in Terminal Renal Failure","volume":"23","author":"Tsujimoto","year":"2008","journal-title":"Drug Metab. Pharmacokinet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/clpt.2009.205","article-title":"The role of organic anion-transporting polypeptides and their common genetic variants in mycophenolic acid pharmacokinetics","volume":"87","author":"Picard","year":"2010","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1097\/00008571-200403000-00003","article-title":"Genetic polymorphisms in the multidrug resistance-associated protein 3 (ABCC3, MRP3) gene and relationship to its mRNA and protein expression in human liver","volume":"14","author":"Lang","year":"2004","journal-title":"Pharmacogenetics"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1097\/00008571-200404000-00001","article-title":"Identification and functional characterization of the natural variant MRP3-Arg1297 His of human multidrug resistance protein 3 (MRP3\/ABCC3)","volume":"14","author":"Lee","year":"2004","journal-title":"Pharmacogenetics"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Renner, O., Harsch, S., Schaeffeler, E., Winter, S., Schwab, M., Krawczyk, M., Rosendahl, J., Wittenburg, H., Lammert, F., and Stange, E.F. (2009). A Variant of the SLC10A2 Gene Encoding the Apical Sodium-Dependent Bile Acid Transporter Is a Risk Factor for Gallstone Disease. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0007321"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1002\/hep.21847","article-title":"Increased gallstone risk in humans conferred by common variant of hepatic ATP-binding cassette transporter for cholesterol","volume":"46","author":"Acalovschi","year":"2007","journal-title":"Hepatology"},{"key":"ref_20","first-page":"170","article-title":"Organic anion transporter protein (OATP1B1) encoded by SLCO1B1 gene polymorphism (388A>G) & susceptibility in gallstone disease","volume":"129","author":"Jindal","year":"2009","journal-title":"Indian J. Med Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1097\/FPC.0b013e32832bcf7b","article-title":"Effect of SLCO1B1 polymorphism on the plasma concentrations of bile acids and bile acid synthesis marker in humans","volume":"19","author":"Xiang","year":"2009","journal-title":"Pharm. Genom."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.arcmed.2006.11.003","article-title":"Apolipoprotein B (APOB) Gene Polymorphism in Patients with Gallbladder Disease","volume":"38","author":"Kurzawski","year":"2007","journal-title":"Arch. Med Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1089\/gte.2007.0067","article-title":"Cholesterol 7\u03b1-hydrolase (CYP7A1) c.-278A>C promoter polymorphism in gallstone disease patients","volume":"12","author":"Juzyszyn","year":"2008","journal-title":"Genet. Test."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1053\/gast.2001.20878","article-title":"Chromosomal organization of candidate genes involved in cholesterol gallstone formation: A murine gallstone map","volume":"120","author":"Lammert","year":"2001","journal-title":"Gastroenterology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7729","DOI":"10.1073\/pnas.92.17.7729","article-title":"Lith1, a major gene affecting cholesterol gallstone formation among inbred strains of mice","volume":"92","author":"Khanuja","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1016\/S0022-2275(20)37422-8","article-title":"Phenotypic characterization of Lith genes that determine susceptibility to cholesterol cholelithiasis in inbred mice: Physical-chemistry of gallbladder bile","volume":"38","author":"Wang","year":"1997","journal-title":"J. Lipid Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.3899\/jrheum.111593","article-title":"ABCB1 and ABCC3 gene polymorphisms are associated with first-year response to methotrexate in juvenile idiopathic arthritis","volume":"39","author":"Bulatovic","year":"2012","journal-title":"J. Rheumatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"100729","DOI":"10.1016\/j.currproblcancer.2021.100729","article-title":"ABCC3 and GSTM5 gene polymorphisms affect overall survival in Polish acute myeloid leukaemia patients","volume":"45","author":"Butrym","year":"2021","journal-title":"Curr. Probl. Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"9388","DOI":"10.18632\/oncotarget.11543","article-title":"Pharmacogenetic analysis of high-dose methotrexate treatment in children with osteosarcoma","volume":"8","author":"Hegyi","year":"2017","journal-title":"Oncotarget"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"de Rotte, M., Pluijm, S., de Jong, P., Bulatovi\u0107 \u0106alasan, M., Wulffraat, N., Weel, A., Lindemans, J., Hazes, J., and de Jonge, R. (2018). Development and validation of a prognostic multivariable model to predict insufficient clinical response to methotrexate in rheumatoid arthritis. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0208534"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"76","DOI":"10.21037\/atm-20-5540","article-title":"Late response to rosuvastatin and statin-related myalgia due to SLCO1B1, SLCO1B3, ABCB11, and CYP3A5 variants in a patient with Familial Hypercholesterolemia: A case report","volume":"9","author":"Faludi","year":"2021","journal-title":"Ann. Transl. Med."},{"key":"ref_32","first-page":"69","article-title":"Impact of SLCO1B3 polymorphisms on clinical outcomes in lung allograft recipients receiving mycophenolic acid","volume":"20","author":"Tague","year":"2020","journal-title":"Pharm. J."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/3\/512\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:36:12Z","timestamp":1760135772000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/3\/512"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,14]]},"references-count":32,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["genes13030512"],"URL":"https:\/\/doi.org\/10.3390\/genes13030512","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,14]]}}}