{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:59:16Z","timestamp":1792803556180,"version":"4.5.0"},"reference-count":103,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T00:00:00Z","timestamp":1649203200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Science and Technology Plan of Beijing Tongzhou District","award":["KJ2020CX006-11"],"award-info":[{"award-number":["KJ2020CX006-11"]}]},{"name":"The Science and Technology Plan of Beijing Tongzhou District","award":["KJ2021CX008-24"],"award-info":[{"award-number":["KJ2021CX008-24"]}]},{"name":"The Science and Technology Plan of Beijing Tongzhou District","award":["KJ2021CX008-22"],"award-info":[{"award-number":["KJ2021CX008-22"]}]},{"name":"Youth Research and Development Fund of Beijing Luhe Hospital, Capital Medical University","award":["LHYY2020-JC10"],"award-info":[{"award-number":["LHYY2020-JC10"]}],"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Gallstone disease is a common pathology of the digestive system with nearly a 10\u201320% incidence rate among adults. The mainstay of treatment is cholecystectomy, which is commonly associated with physical pain and may also seriously affect a patient\u2019s quality of life. Clinical research suggests that cholelithiasis is closely related to the age, gender, body mass index, and other basic physical characteristics of patients. Clinical research further suggests that the occurrence of cholelithiasis is related to obesity, diabetes, non-alcoholic fatty liver, and other diseases. For this reason, we reviewed the following: genetic factors; excessive liver cholesterol secretion (causing cholesterol supersaturation in gallbladder bile); accelerated growth of cholesterol crystals and solid cholesterol crystals; gallbladder motility impairment; and cardiovascular factors. Herein, we summarize and analyze the causes and mechanisms of cholelithiasis, discuss its correlation with the pathogenesis of related diseases, and discuss possible mechanisms.<\/jats:p>","DOI":"10.3390\/biom12040550","type":"journal-article","created":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T16:21:30Z","timestamp":1649262090000},"page":"550","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":193,"title":["Factors Influencing Gallstone Formation: A Review of the Literature"],"prefix":"10.3390","volume":"12","author":[{"given":"Hao","family":"Sun","sequence":"first","affiliation":[{"name":"Central Laboratories, Beijing Luhe Clinical Institute, Capital Medical University, Beijing 101199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7205-7191","authenticated-orcid":false,"given":"Jonathan","family":"Warren","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Yip","sequence":"additional","affiliation":[{"name":"Department of Pathology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96831, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Ji","sequence":"additional","affiliation":[{"name":"Central Laboratories, Beijing Luhe Clinical Institute, Capital Medical University, Beijing 101199, China"},{"name":"Department of General Surgery, Beijing Luhe Clinical Institute, Capital Medical University, Beijing 101199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaolong","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Beijing Luhe Clinical Institute, Capital Medical University, Beijing 101199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Han","sequence":"additional","affiliation":[{"name":"Central Laboratories, Beijing Luhe Clinical Institute, Capital Medical University, Beijing 101199, China"},{"name":"Department of General Surgery, Beijing Luhe Clinical Institute, Capital Medical University, Beijing 101199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchuan","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI 48201, USA"},{"name":"John D. Dingell VA Medical Center, 4646 John R Street, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1016\/j.jhep.2018.08.025","article-title":"Claudin-3 regulates bile canalicular paracellular barrier and cholesterol gallstone core formation in mice","volume":"69","author":"Tanaka","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"9730687","DOI":"10.1155\/2016\/9730687","article-title":"Abdominal Symptoms and Incident Gallstones in a Population Unaware of Gallstone Status","volume":"2016","author":"Shabanzadeh","year":"2016","journal-title":"Can. J. Gastroenterol. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1002\/hep.31537","article-title":"Gallstones, Body Mass Index, C-Reactive Protein, and Gallbladder Cancer: Mendelian Randomization Analysis of Chilean and European Genotype Data","volume":"73","author":"Scherer","year":"2021","journal-title":"Hepatology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.gtc.2010.02.007","article-title":"Lith genes and genetic analysis of cholesterol gallstone formation","volume":"39","author":"Wang","year":"2010","journal-title":"Gastroenterol. Clin."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"269","DOI":"10.15557\/JoU.2019.0040","article-title":"Gallbladder diseases in pregnancy: Sonographic findings in an indigenous African population","volume":"19","author":"Idowu","year":"2019","journal-title":"J. Ultrason."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1111\/andr.12391","article-title":"Are incident gallstones associated to sex-dependent changes with age? A cohort Study","volume":"5","author":"Shabanzadeh","year":"2017","journal-title":"Andrology"},{"key":"ref_7","first-page":"257","article-title":"Factors that influence bile fluid microbiology in cholecystectomized patients","volume":"85","year":"2020","journal-title":"Rev. Gastroenterol. Mex."},{"key":"ref_8","first-page":"1751","article-title":"The integrity of the cholecystokinin receptor gene in gallbladder disease and obesity","volume":"22","author":"Nardone","year":"1995","journal-title":"Hepatology"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Qiao, T., Ma, R.H., Luo, X.B., Yang, L.Q., Luo, Z.L., and Zheng, P.M. (2013). The systematic classification of gallbladder stones. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0074887"},{"key":"ref_10","first-page":"488","article-title":"Calcium carbonate in cholesterol gallstones: Polymorphism, distribution, and hypotheses about pathogenesis","volume":"22","author":"Taylor","year":"1995","journal-title":"Hepatology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1007\/s004230100220","article-title":"Carcinogenesis of malignant lesions of the gall bladder. The impact of chronic inflammation and gallstones","volume":"386","author":"Tazuma","year":"2001","journal-title":"Langenbecks Arch. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.immuni.2019.07.002","article-title":"Neutrophil Extracellular Traps Initiate Gallstone Formation","volume":"51","author":"Munoz","year":"2019","journal-title":"Immunity"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1038\/s41586-020-2928-y","article-title":"Feeding induces cholesterol biosynthesis via the mTORC1-USP20-HMGCR axis","volume":"588","author":"Lu","year":"2020","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1016\/j.jacc.2014.02.553","article-title":"Opposing effects of ABCG5\/8 function on myocardial infarction and gallstone disease","volume":"63","author":"Rader","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1093\/eurheartj\/ehab644","article-title":"Propionate attenuates atherosclerosis by immune-dependent regulation of intestinal cholesterol metabolism","volume":"43","author":"Haghikia","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"C916","DOI":"10.1152\/ajpcell.00062.2021","article-title":"NPC1L1-dependent transport of 27-alkyne cholesterol in intestinal epithelial cells","volume":"320","author":"Ticho","year":"2021","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Chambers, K.F., Day, P.E., Aboufarrag, H.T., and Kroon, P.A. (2019). Polyphenol Effects on Cholesterol Metabolism via Bile Acid Biosynthesis, CYP7A1: A Review. Nutrients, 11.","DOI":"10.3390\/nu11112588"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.jhep.2016.08.017","article-title":"Metabolic preconditioning protects BSEP\/ABCB11(-\/-) mice against cholestatic liver injury","volume":"66","author":"Fuchs","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.jconrel.2020.07.034","article-title":"Bile acid transporter-mediated oral drug delivery","volume":"327","author":"Deng","year":"2020","journal-title":"J. Control. Release"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e00287","DOI":"10.1002\/prp2.287","article-title":"Influence of age on intestinal bile acid transport in C57BL\/6 mice","volume":"5","author":"Gao","year":"2017","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.pharmthera.2018.10.007","article-title":"Organic Anion Transporting Polypeptide (OATP) transporter expression, localization and function in the human intestine","volume":"195","author":"Oswald","year":"2019","journal-title":"Pharmacol. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3915","DOI":"10.12998\/wjcc.v7.i23.3915","article-title":"Overview of organic anion transporters and organic anion transporter polypeptides and their roles in the liver","volume":"7","author":"Li","year":"2019","journal-title":"World J. Clin. Cases"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.1007\/s10620-016-4125-2","article-title":"Significant Association Between Gallstone Disease and Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis","volume":"61","author":"Jaruvongvanich","year":"2016","journal-title":"Dig. Dis. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Grigor\u2019eva, I.N., and Romanova, T.I. (2020). Gallstone Disease and Microbiome. Microorganisms, 8.","DOI":"10.3390\/microorganisms8060835"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1097\/MOG.0000000000000417","article-title":"Mouse models of gallstone disease","volume":"34","author":"Wang","year":"2018","journal-title":"Curr. Opin. Gastroenterol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1194\/jlr.M054544","article-title":"Relative roles of ABCG5\/ABCG8 in liver and intestine","volume":"56","author":"Wang","year":"2015","journal-title":"J. Lipid Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/978-981-15-6082-8_8","article-title":"Recent Advances in the Critical Role of the Sterol Efflux Transporters ABCG5\/G8 in Health and Disease","volume":"1276","author":"Wang","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/j.1365-2362.1980.tb00006.x","article-title":"Phytosterolaemia, xanthomatosis and premature atherosclerotic arterial disease: A case with high plant sterol absorption, impaired sterol elimination and low cholesterol synthesis","volume":"10","author":"Miettinen","year":"1980","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1126\/science.290.5497.1771","article-title":"Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters","volume":"290","author":"Berge","year":"2000","journal-title":"Science"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/83799","article-title":"Identification of a gene, ABCG5, important in the regulation of dietary cholesterol absorption","volume":"27","author":"Lee","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Wang, H.H., Portincasa, P., Liu, M., Tso, P., and Wang, D.Q. (2020). An Update on the Lithogenic Mechanisms of Cholecystokinin a Receptor (CCKAR), an Important Gallstone Gene for Lith13. Genes, 11.","DOI":"10.3390\/genes11121438"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3407","DOI":"10.2174\/0929867324666170619104801","article-title":"Update on the Molecular Mechanisms Underlying the Effect of Cholecystokinin and Cholecystokinin-1 Receptor on the Formation of Cholesterol Gallstones","volume":"26","author":"Wang","year":"2019","journal-title":"Curr. Med. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"40","DOI":"10.2967\/jnmt.119.233486","article-title":"Kinetics of Gallbladder Emptying During Cholecystokinin Cholescintigraphy as an Indicator of In Vivo Hormonal Sensitivity","volume":"48","author":"Miller","year":"2020","journal-title":"J. Nucl. Med. Technol."},{"key":"ref_34","first-page":"V05180386","article-title":"Effects of glucagon-like peptides on gallbladder motility","volume":"180","author":"Gether","year":"2018","journal-title":"Ugeskr Laeger"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.molmet.2017.03.006","article-title":"Glucagon-like peptide-2 promotes gallbladder refilling via a TGR5-independent, GLP-2R-dependent pathway","volume":"6","author":"Yusta","year":"2017","journal-title":"Mol. Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1080\/09674845.2014.11669957","article-title":"Detection of Helicobacter pylori infection in Egyptian patients with chronic calcular cholecystitis","volume":"71","author":"Helaly","year":"2014","journal-title":"Br. J. Biomed. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1111\/j.1365-2036.2005.02644.x","article-title":"DNA sequences and proteic antigens of H. pylori in cholecystic bile and tissue of patients with gallstones","volume":"22","author":"Neri","year":"2005","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1053\/j.gastro.2005.01.008","article-title":"Identification of cholelithogenic enterohepatic helicobacter species and their role in murine cholesterol gallstone formation","volume":"128","author":"Maurer","year":"2005","journal-title":"Gastroenterology"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Antharam, V.C., McEwen, D.C., Garrett, T.J., Dossey, A.T., Li, E.C., Kozlov, A.N., Mesbah, Z., and Wang, G.P. (2016). An Integrated Metabolomic and Microbiome Analysis Identified Specific Gut Microbiota Associated with Fecal Cholesterol and Coprostanol in Clostridium difficile Infection. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0148824"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1016\/j.amjsurg.2006.08.001","article-title":"Biliary bacterial factors determine the path of gallstone formation","volume":"192","author":"Stewart","year":"2006","journal-title":"Am. J. Surg."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1007\/s10096-016-2669-x","article-title":"Association of diverse bacterial communities in human bile samples with biliary tract disorders: A survey using culture and polymerase chain reaction-denaturing gradient gel electrophoresis methods","volume":"35","author":"Tajeddin","year":"2016","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1097\/00000658-198709000-00002","article-title":"Pigment gallstones form as a composite of bacterial microcolonies and pigment solids","volume":"206","author":"Stewart","year":"1987","journal-title":"Ann. Surg."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4347","DOI":"10.1038\/s41598-020-60081-8","article-title":"Author Correction: Metagenomics of pigmented and cholesterol gallstones: The putative role of bacteria","volume":"10","author":"Kose","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"643109","DOI":"10.1155\/2013\/643109","article-title":"Gallstones and Concomitant Gastric Helicobacter pylori Infection","volume":"2013","author":"Attaallah","year":"2013","journal-title":"Gastroenterol. Res. Pract."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4296","DOI":"10.4049\/jimmunol.178.7.4296","article-title":"Activation of enteroendocrine cells via TLRs induces hormone, chemokine, and defensin secretion","volume":"178","author":"Palazzo","year":"2007","journal-title":"J. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Fremont-Rahl, J.J., Ge, Z., Umana, C., Whary, M.T., Taylor, N.S., Muthupalani, S., Carey, M.C., Fox, J.G., and Maurer, K.J. (2013). An analysis of the role of the indigenous microbiota in cholesterol gallstone pathogenesis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0070657"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"G175","DOI":"10.1152\/ajpgi.00272.2005","article-title":"Helicobacter pylori and cholesterol gallstone formation in C57L\/J mice: A prospective study","volume":"290","author":"Maurer","year":"2006","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1080\/003655202753387455","article-title":"Identification of Helicobacter pylori DNA in human cholesterol gallstones","volume":"37","author":"Monstein","year":"2002","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1097\/00000658-198905000-00011","article-title":"The role of bacteria in gallbladder and common duct stone formation","volume":"209","author":"Kaufman","year":"1989","journal-title":"Ann. Surg."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1111\/1758-2229.12319","article-title":"Interactions between the intestinal microbiota and bile acids in gallstones patients","volume":"7","author":"Keren","year":"2015","journal-title":"Environ. Microbiol. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Wu, T., Zhang, Z., Liu, B., Hou, D., Liang, Y., Zhang, J., and Shi, P. (2013). Gut microbiota dysbiosis and bacterial community assembly associated with cholesterol gallstones in large-scale study. BMC Genom., 14.","DOI":"10.1186\/1471-2164-14-669"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.cmet.2005.09.001","article-title":"Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis","volume":"2","author":"Inagaki","year":"2005","journal-title":"Cell Metab."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1002\/hep.20776","article-title":"Is the FXR the fix for cholesterol gallstone disease?","volume":"42","author":"Juran","year":"2005","journal-title":"Hepatology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"185","DOI":"10.3389\/fphys.2019.00185","article-title":"Intestinal Bacteria Interplay with Bile and Cholesterol Metabolism: Implications on Host Physiology","volume":"10","author":"Molinero","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1038\/s41385-019-0162-4","article-title":"Emerging roles of bile acids in mucosal immunity and inflammation","volume":"12","author":"Chen","year":"2019","journal-title":"Mucosal Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.12688\/f1000research.15505.1","article-title":"Recent advances in understanding and managing cholesterol gallstones","volume":"7","author":"Portincasa","year":"2018","journal-title":"F1000Research"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5742","DOI":"10.1128\/AEM.02806-06","article-title":"Bacteroides sp. strain D8, the first cholesterol-reducing bacterium isolated from human feces","volume":"73","author":"Gerard","year":"2007","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e9679","DOI":"10.1097\/MD.0000000000009679","article-title":"The effects of probiotics on total cholesterol: A meta-analysis of randomized controlled trials","volume":"97","author":"Wang","year":"2018","journal-title":"Medicine"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1017\/S0007114511004703","article-title":"Cholesterol-lowering efficacy of a microencapsulated bile salt hydrolase-active Lactobacillus reuteri NCIMB 30242 yoghurt formulation in hypercholesterolaemic adults","volume":"107","author":"Jones","year":"2012","journal-title":"Br. J. Nutr."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2410","DOI":"10.1001\/jama.2021.4502","article-title":"Gallstones in Pregnancy","volume":"325","author":"Celaj","year":"2021","journal-title":"JAMA"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1001\/jamasurg.2021.0643","article-title":"Nonoperative Management for Pregnant Individuals with Gallstone Disease in the Third Trimester-Reply","volume":"156","author":"Schwulst","year":"2021","journal-title":"JAMA Surg."},{"key":"ref_62","first-page":"112","article-title":"Gall stone in pregnancy","volume":"12","author":"Hossain","year":"2003","journal-title":"Mymensingh Med. J."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1097\/GRF.0000000000000496","article-title":"Gallbladder and Biliary Disease in Pregnancy","volume":"63","author":"Brown","year":"2020","journal-title":"Clin. Obstet. Gynecol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/S0960-0760(00)00104-7","article-title":"Molecular mechanisms of estrogen action: Selective ligands and receptor pharmacology","volume":"74","author":"Katzenellenbogen","year":"2000","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/ng0702-235","article-title":"From QTL to gene: The harvest begins","volume":"31","author":"Korstanje","year":"2002","journal-title":"Nat. Genet."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1126\/science.8091226","article-title":"Genetic dissection of complex traits","volume":"265","author":"Lander","year":"1994","journal-title":"Science"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Boston Collaborative Drug Surveillance Program, Boston University Medical Center (1974). Surgically confirmed gallbladder disease, venous thromboembolism, and breast tumors in relation to postmenopausal estrogen therapy. N. Engl. J. Med., 290, 15\u201319.","DOI":"10.1056\/NEJM197401032900104"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1056\/NEJM197601222940403","article-title":"Effects of oral contraceptives on the gallbladder bile of normal women","volume":"294","author":"Bennion","year":"1976","journal-title":"N. Engl. J. Med."},{"key":"ref_69","first-page":"207","article-title":"A prospective study of symptomatic gallstones in women: Relation with oral contraceptives and other risk factors","volume":"84","author":"Grodstein","year":"1994","journal-title":"Obstet. Gynecol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/0016-5085(88)90614-2","article-title":"Increased risk of cholecystectomy in users of supplemental estrogen","volume":"94","author":"Petitti","year":"1988","journal-title":"Gastroenterology"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1194\/jlr.M500454-JLR200","article-title":"Overexpression of estrogen receptor alpha increases hepatic cholesterogenesis, leading to biliary hypersecretion in mice","volume":"47","author":"Wang","year":"2006","journal-title":"J. Lipid Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1053\/j.gastro.2006.10.024","article-title":"Cholesterol gallstone susceptibility loci: A mouse map, candidate gene evaluation, and guide to human LITH genes","volume":"131","author":"Lyons","year":"2006","journal-title":"Gastroenterology"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1055\/s-0031-1276645","article-title":"Dissecting the genetic heterogeneity of gallbladder stone formation","volume":"31","author":"Krawczyk","year":"2011","journal-title":"Semin. Liver Dis."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1006\/geno.1997.4972","article-title":"Identification of a gene (GPR30) with homology to the G-protein-coupled receptor superfamily associated with estrogen receptor expression in breast cancer","volume":"45","author":"Carmeci","year":"1997","journal-title":"Genomics"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1194\/jlr.M059121","article-title":"Estrogen induces two distinct cholesterol crystallization pathways by activating ERalpha and GPR30 in female mice","volume":"56","author":"Wang","year":"2015","journal-title":"J. Lipid Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1002\/ijc.29519","article-title":"HIF-1 at the crossroads of hypoxia, inflammation, and cancer","volume":"138","author":"Balamurugan","year":"2016","journal-title":"Int. J. Cancer"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1183\/13993003.01929-2019","article-title":"Roles of HIF1 and HIF2 in pulmonary hypertension: It all depends on the context","volume":"54","author":"Waypa","year":"2019","journal-title":"Eur. Respir. J."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/978-1-4419-1241-1_10","article-title":"Fenofibrate, a peroxisome proliferator-activated receptor alpha agonist, improves hepatic microcirculatory patency and oxygen availability in a high-fat-diet-induced fatty liver in mice","volume":"662","author":"Kondo","year":"2010","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1007\/s11033-018-4320-7","article-title":"Investigate of AQP gene expression in the liver of mice after ischemia-reperfusion","volume":"45","author":"Karimi","year":"2018","journal-title":"Mol. Biol. Rep."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1002\/hep.1840380421","article-title":"Ontogeny, distribution, and possible functional implications of an unusual aquaporin, AQP8, in mouse liver","volume":"38","author":"Ferri","year":"2003","journal-title":"Hepatology"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"137","DOI":"10.2174\/1568008054064850","article-title":"Water transport into bile and role in bile formation","volume":"5","author":"Calamita","year":"2005","journal-title":"Curr. Drug Targets Immune Endocr. Metabol. Disord."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1097\/MOG.0000000000000416","article-title":"Nonalcoholic fatty liver disease, cholesterol gallstones, and cholecystectomy: New insights on a complex relationship","volume":"34","author":"Arrese","year":"2018","journal-title":"Curr. Opin. Gastroenterol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.jhep.2016.03.005","article-title":"EASL Clinical Practice Guidelines on the prevention, diagnosis and treatment of gallstones","volume":"65","author":"Lammert","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1038\/ajg.2013.84","article-title":"Cholecystectomy and NAFLD: Does gallbladder removal have metabolic consequences?","volume":"108","author":"Nervi","year":"2013","journal-title":"Am. J. Gastroenterol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.1016\/j.jacc.2013.12.055","article-title":"The ABCG5\/8 cholesterol transporter and myocardial infarction versus gallstone disease","volume":"63","author":"Stender","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2618","DOI":"10.1093\/eurheartj\/ehaa531","article-title":"Genetic variability in the absorption of dietary sterols affects the risk of coronary artery disease","volume":"41","author":"Helgadottir","year":"2020","journal-title":"Eur. Heart J."},{"key":"ref_87","first-page":"3092","article-title":"Association between gallstone and cardio-cerebrovascular disease: Systematic review and meta-analysis","volume":"17","author":"Zhao","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1007\/s10654-017-0263-x","article-title":"Screen-detected gallstone disease and cardiovascular disease","volume":"32","author":"Shabanzadeh","year":"2017","journal-title":"Eur. J. Epidemiol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.7754\/Clin.Lab.2015.150219","article-title":"Metabolic Syndrome, Independent Predictor for Coronary Artery Disease","volume":"61","author":"Zidi","year":"2015","journal-title":"Clin. Lab."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"4215","DOI":"10.3748\/wjg.v18.i31.4215","article-title":"Metabolic syndrome and gallstone disease","volume":"18","author":"Chen","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.1161\/ATVBAHA.115.306339","article-title":"Gallstone Disease and Increased Risk of Ischemic Heart Disease: Causal Association or Epiphenomenon?","volume":"35","author":"Targher","year":"2015","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.numecd.2019.09.008","article-title":"Worldwide burden of LDL cholesterol: Implications in cardiovascular disease","volume":"30","author":"Mattiuzzi","year":"2020","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Yamanashi, Y., Takada, T., Yamamoto, H., and Suzuki, H. (2020). NPC1L1 Facilitates Sphingomyelin Absorption and Regulates Diet-Induced Production of VLDL\/LDL-associated S1P. Nutrients, 12.","DOI":"10.3390\/nu12092641"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1126\/science.1093131","article-title":"Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption","volume":"303","author":"Altmann","year":"2004","journal-title":"Science"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1124\/jpet.106.114181","article-title":"Niemann-Pick C1-like 1 overexpression facilitates ezetimibe-sensitive cholesterol and beta-sitosterol uptake in CaCo-2 cells","volume":"320","author":"Yamanashi","year":"2007","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"8132","DOI":"10.1073\/pnas.0500269102","article-title":"The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1)","volume":"102","author":"Lisnock","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1093\/eurheartj\/ehv108","article-title":"Genetic variation in the cholesterol transporter NPC1L1, ischaemic vascular disease, and gallstone disease","volume":"36","author":"Lauridsen","year":"2015","journal-title":"Eur. Heart J."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"3898","DOI":"10.1111\/bph.13818","article-title":"Targeting inflammation to reduce cardiovascular disease risk: A realistic clinical prospect?","volume":"174","author":"Welsh","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1111\/jth.13142","article-title":"Does deficiency of von Willebrand factor protect against cardiovascular disease? Analysis of a national discharge register","volume":"13","author":"Seaman","year":"2015","journal-title":"J. Thromb. Haemost."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2643","DOI":"10.1007\/s00464-021-08989-8","article-title":"Original contribution: Sleeve gastrectomy reduces soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) levels in patients with morbid obesity","volume":"36","author":"Taskin","year":"2022","journal-title":"Surg. Endosc."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"e003421","DOI":"10.1161\/CIRCGEN.121.003421","article-title":"Soluble Urokinase Plasminogen Activator Receptor: Genetic Variation and Cardiovascular Disease Risk in Black Adults","volume":"14","author":"Olson","year":"2021","journal-title":"Circ. Genom. Precis. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"17","DOI":"10.21037\/jlpm.2020.03.03","article-title":"GlycA: A New Biomarker for Systemic Inflammation and Cardiovascular Disease (CVD) Risk Assessment","volume":"5","author":"Ballout","year":"2020","journal-title":"J. Lab. Precis. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.mayocpiqo.2018.01.002","article-title":"Epidemiologic Factors, Clinical Presentation, Causes, and Outcomes of Liver Abscess: A 35-Year Olmsted County Study","volume":"2","author":"Sharma","year":"2018","journal-title":"Mayo Clin. Proc. Innov. Qual. Outcomes"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/4\/550\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:49:20Z","timestamp":1760136560000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/4\/550"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,6]]},"references-count":103,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["biom12040550"],"URL":"https:\/\/doi.org\/10.3390\/biom12040550","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,6]]}}}