{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:51:57Z","timestamp":1790272317220,"version":"4.1.0"},"reference-count":75,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T00:00:00Z","timestamp":1679270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008108","name":"Buddhist Tzu Chi Medical Foundation","doi-asserted-by":"publisher","award":["TCMF-EP 111-02"],"award-info":[{"award-number":["TCMF-EP 111-02"]}],"id":[{"id":"10.13039\/501100008108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008108","name":"Buddhist Tzu Chi Medical Foundation","doi-asserted-by":"publisher","award":["TCRD-TPE-112-02"],"award-info":[{"award-number":["TCRD-TPE-112-02"]}],"id":[{"id":"10.13039\/501100008108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008108","name":"Buddhist Tzu Chi Medical Foundation","doi-asserted-by":"publisher","award":["TCMF-A 112-02"],"award-info":[{"award-number":["TCMF-A 112-02"]}],"id":[{"id":"10.13039\/501100008108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008108","name":"Buddhist Tzu Chi Medical Foundation","doi-asserted-by":"publisher","award":["TCRD-TPE-112-31"],"award-info":[{"award-number":["TCRD-TPE-112-31"]}],"id":[{"id":"10.13039\/501100008108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008108","name":"Buddhist Tzu Chi Medical Foundation","doi-asserted-by":"publisher","award":["TCRD-TPE-109-RT-1"],"award-info":[{"award-number":["TCRD-TPE-109-RT-1"]}],"id":[{"id":"10.13039\/501100008108","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Taipei Tzu Chi Hospital","award":["TCMF-EP 111-02"],"award-info":[{"award-number":["TCMF-EP 111-02"]}]},{"name":"Taipei Tzu Chi Hospital","award":["TCRD-TPE-112-02"],"award-info":[{"award-number":["TCRD-TPE-112-02"]}]},{"name":"Taipei Tzu Chi Hospital","award":["TCMF-A 112-02"],"award-info":[{"award-number":["TCMF-A 112-02"]}]},{"name":"Taipei Tzu Chi Hospital","award":["TCRD-TPE-112-31"],"award-info":[{"award-number":["TCRD-TPE-112-31"]}]},{"name":"Taipei Tzu Chi Hospital","award":["TCRD-TPE-109-RT-1"],"award-info":[{"award-number":["TCRD-TPE-109-RT-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>ABCG5 and ABCG8 are two key adenosine triphosphate-binding cassette (ABC) proteins that regulate whole-body sterol trafficking. This study aimed to elucidate the association between ABCG5\/G8 gene region variants and lipid profile, cardiometabolic traits, and gallstone disease history in Taiwan. A total of 1494 Taiwan Biobank participants with whole-genome sequencing data and 117,679 participants with Axiom Genome-Wide CHB Array data were enrolled for analysis. Using genotype\u2013phenotype and stepwise linear regression analyses, we found independent associations of four Asian-specific ABCG5 variants, rs119480069, rs199984328, rs560839317, and rs748096191, with total, low-density lipoprotein (LDL), and non-high-density lipoprotein (HDL) cholesterol levels (all p \u2264 0.0002). Four other variants, which were in nearly complete linkage disequilibrium, exhibited genome-wide significant associations with gallstone disease history, and the ABCG8 rs11887534 variant showed a trend of superiority for gallstone disease history in a nested logistic regression model (p = 0.074). Through regional association analysis of various other cardiometabolic traits, two variants of the PLEKHH2, approximately 50 kb from the ABCG5\/G8 region, exhibited significant associations with blood pressure status (p &lt; 10\u22126). In conclusion, differential effects of ABCG5\/G8 region variants were noted for lipid profile, blood pressure status, and gallstone disease history in Taiwan. These results indicate the crucial role of individualized assessment of ABCG5\/G8 variants for different cardiometabolic phenotypes.<\/jats:p>","DOI":"10.3390\/genes14030754","type":"journal-article","created":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T03:15:03Z","timestamp":1679368503000},"page":"754","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Differential Effects of ABCG5\/G8 Gene Region Variants on Lipid Profile, Blood Pressure Status, and Gallstone Disease History in Taiwan"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4140-5699","authenticated-orcid":false,"given":"Ming-Sheng","family":"Teng","sequence":"first","affiliation":[{"name":"Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuan-Hung","family":"Yeh","sequence":"additional","affiliation":[{"name":"Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, Taiwan"},{"name":"School of Medicine, Tzu Chi University, Hualien 97004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0012-2804","authenticated-orcid":false,"given":"Lung-An","family":"Hsu","sequence":"additional","affiliation":[{"name":"The First Cardiovascular Division, Department of Internal Medicine, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan 33305, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin-Hua","family":"Chou","sequence":"additional","affiliation":[{"name":"Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, Taiwan"},{"name":"School of Medicine, Tzu Chi University, Hualien 97004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leay-Kiaw","family":"Er","sequence":"additional","affiliation":[{"name":"School of Medicine, Tzu Chi University, Hualien 97004, Taiwan"},{"name":"The Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Semon","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Life Science, Chinese Culture University, Taipei 11114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8218-6827","authenticated-orcid":false,"given":"Yu-Lin","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, Taiwan"},{"name":"Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, Taiwan"},{"name":"School of Medicine, Tzu Chi University, Hualien 97004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/978-981-13-7647-4_2","article-title":"ABC Family Transporters","volume":"1141","author":"Liu","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1146\/annurev-biochem-011520-105201","article-title":"Structural and Mechanistic Principles of ABC Transporters","volume":"89","author":"Thomas","year":"2020","journal-title":"Annu. Rev. Biochem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1146\/annurev-physiol-031620-094944","article-title":"The ABCs of Sterol Transport","volume":"83","author":"Plummer","year":"2021","journal-title":"Annu. Rev. Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Schumacher, T., and Benndorf, R.A. (2017). ABC Transport Proteins in Cardiovascular Disease-A Brief Summary. Molecules, 22.","DOI":"10.3390\/molecules22040589"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1194\/jlr.R084244","article-title":"ABCG5 and ABCG8: More than a defense against xenosterols","volume":"59","author":"Patel","year":"2018","journal-title":"J. Lipid Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1146\/annurev.physiol.69.031905.160725","article-title":"Regulation of intestinal cholesterol absorption","volume":"69","author":"Wang","year":"2007","journal-title":"Annu. Rev. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1172\/JCI0216000","article-title":"Coexpression of ATP-binding cassette proteins ABCG5 and ABCG8 permits their transport to the apical surface","volume":"110","author":"Graf","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"48275","DOI":"10.1074\/jbc.M310223200","article-title":"ABCG5 and ABCG8 are obligate heterodimers for protein trafficking and biliary cholesterol excretion","volume":"278","author":"Graf","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_9","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_10","doi-asserted-by":"crossref","first-page":"4507","DOI":"10.1074\/jbc.M512277200","article-title":"Functional asymmetry of nucleotide-binding domains in ABCG5 and ABCG8","volume":"281","author":"Zhang","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1016\/j.jacl.2018.08.006","article-title":"Oligogenic familial hypercholesterolemia, LDL cholesterol, and coronary artery disease","volume":"12","author":"Tada","year":"2018","journal-title":"J. Clin. Lipidol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1086\/321294","article-title":"Two genes that map to the STSL locus cause sitosterolemia: Genomic structure and spectrum of mutations involving sterolin-1 and sterolin-2, encoded by ABCG5 and ABCG8, respectively","volume":"69","author":"Lu","year":"2001","journal-title":"Am. J. Hum. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s10545-010-9126-2","article-title":"Clinical observations, molecular genetic analysis, and treatment of sitosterolemia in infants and children","volume":"33","author":"Niu","year":"2010","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_14","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_15","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. N. Am."},{"key":"ref_16","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_17","doi-asserted-by":"crossref","unstructured":"Williams, K., Segard, A., and Graf, G.A. (2021). Sitosterolemia: Twenty Years of Discovery of the Function of ABCG5ABCG8. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052641"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1016\/S0016-5085(03)01053-9","article-title":"FXR and ABCG5\/ABCG8 as determinants of cholesterol gallstone formation from quantitative trait locus mapping in mice","volume":"125","author":"Wittenburg","year":"2003","journal-title":"Gastroenterology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1053\/j.gastro.2003.10.074","article-title":"Sitosterolemia in ABC-transporter G5-deficient mice is aggravated on activation of the liver-X receptor","volume":"126","author":"Bloks","year":"2004","journal-title":"Gastroenterology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1002\/hep.21579","article-title":"Quantifying anomalous intestinal sterol uptake, lymphatic transport, and biliary secretion in Abcg8(-\/-) mice","volume":"45","author":"Wang","year":"2007","journal-title":"Hepatology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"16237","DOI":"10.1073\/pnas.252582399","article-title":"Disruption of Abcg5 and Abcg8 in mice reveals their crucial role in biliary cholesterol secretion","volume":"99","author":"Yu","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1172\/JCI0216001","article-title":"Overexpression of ABCG5 and ABCG8 promotes biliary cholesterol secretion and reduces fractional absorption of dietary cholesterol","volume":"110","author":"Yu","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Chen, J., Batta, A., Zheng, S., Fitzgibbon, W.R., Ullian, M.E., Yu, H., Tso, P., Salen, G., and Patel, S.B. (2005). The missense mutation in Abcg5 gene in spontaneously hypertensive rats (SHR) segregates with phytosterolemia but not hypertension. BMC Genet., 6.","DOI":"10.1186\/1471-2156-6-40"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1007\/s10038-008-0310-2","article-title":"Significant association of ABCG8:D19H gene polymorphism with hypercholesterolemia and insulin resistance","volume":"53","author":"Chen","year":"2008","journal-title":"J. Hum. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.atherosclerosis.2010.01.010","article-title":"Genetic variations at ABCG5\/G8 genes modulate plasma lipids concentrations in patients with familial hypercholesterolemia","volume":"210","author":"Fuentes","year":"2010","journal-title":"Atherosclerosis"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1194\/jlr.M300522-JLR200","article-title":"Polymorphisms in the ABCG5 and ABCG8 genes associate with cholesterol absorption and insulin sensitivity","volume":"45","author":"Gylling","year":"2004","journal-title":"J. Lipid Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1016\/j.bbalip.2011.07.019","article-title":"ATP-binding cassette G5\/G8 deficiency causes hypertriglyceridemia by affecting multiple metabolic pathways","volume":"1811","author":"Julve","year":"2011","journal-title":"Biochim. Et Biophys. Acta"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"28564","DOI":"10.1074\/jbc.M112.360081","article-title":"The ABCG5 ABCG8 sterol transporter opposes the development of fatty liver disease and loss of glycemic control independently of phytosterol accumulation","volume":"287","author":"Su","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1161\/ATVBAHA.113.302355","article-title":"Acceleration of biliary cholesterol secretion restores glycemic control and alleviates hypertriglyceridemia in obese db\/db mice","volume":"34","author":"Su","year":"2014","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Yu, H., Pandit, B., Klett, E., Lee, M.H., Lu, K., Helou, K., Ikeda, I., Egashira, N., Sato, M., and Klein, R. (2003). The rat STSL locus: Characterization, chromosomal assignment, and genetic variations in sitosterolemic hypertensive rats. BMC Cardiovasc. Disord., 3.","DOI":"10.1186\/1471-2261-3-4"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/nature19057","article-title":"Analysis of protein-coding genetic variation in 60,706 humans","volume":"536","author":"Lek","year":"2016","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"24881","DOI":"10.1074\/jbc.M402634200","article-title":"Missense mutations in ABCG5 and ABCG8 disrupt heterodimerization and trafficking","volume":"279","author":"Graf","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1161\/CIRCGEN.119.002871","article-title":"Heterozygous ABCG5 Gene Deficiency and Risk of Coronary Artery Disease","volume":"13","author":"Nomura","year":"2020","journal-title":"Circ. Genom. Precis. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/s41467-021-27706-6","article-title":"Genome-wide meta-analysis of phytosterols reveals five novel loci and a detrimental effect on coronary atherosclerosis","volume":"13","author":"Scholz","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_35","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_36","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1002\/bjs.6178","article-title":"Significant association of ABCG5 604Q and ABCG8 D19H polymorphisms with gallstone disease","volume":"95","author":"Kuo","year":"2008","journal-title":"Br. J. Surg."},{"key":"ref_37","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_38","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1038\/nrg3604","article-title":"Recent human adaptation: Genomic approaches, interpretation and insights","volume":"14","author":"Scheinfeldt","year":"2013","journal-title":"Nat. Reviews. Genet."},{"key":"ref_39","first-page":"5321","article-title":"Population structure of Han Chinese in the modern Taiwanese population based on 10,000 participants in the Taiwan Biobank project","volume":"25","author":"Chen","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.jare.2020.12.003","article-title":"Rare variants discovery by extensive whole-genome sequencing of the Han Chinese population in Taiwan: Applications to cardiovascular medicine","volume":"30","author":"Juang","year":"2021","journal-title":"J. Adv. Res."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Hsu, L.A., Teng, M.S., Wu, S., Chou, H.H., and Ko, Y.L. (2022). Common and Rare PCSK9 Variants Associated with Low-Density Lipoprotein Cholesterol Levels and the Risk of Diabetes Mellitus: A Mendelian Randomization Study. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231810418"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Yeh, K.H., Hsu, L.A., Teng, M.S., Wu, S., Chou, H.H., and Ko, Y.L. (2022). Pleiotropic Effects of Common and Rare GCKR Exonic Mutations on Cardiometabolic Traits. Genes, 13.","DOI":"10.3390\/genes13030491"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Yeh, K.H., Wan, H.L., Teng, M.S., Chou, H.H., Hsu, L.A., and Ko, Y.L. (2022). Genetic Variants at the APOE Locus Predict Cardiometabolic Traits and Metabolic Syndrome: A Taiwan Biobank Study. Genes, 13.","DOI":"10.3390\/genes13081366"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1093\/bioinformatics\/btt314","article-title":"Isaac: Ultra-fast whole-genome secondary analysis on Illumina sequencing platforms","volume":"29","author":"Raczy","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"508","DOI":"10.2337\/dbi19-0007","article-title":"Remnants of the Triglyceride-Rich Lipoproteins, Diabetes, and Cardiovascular Disease","volume":"69","author":"Chait","year":"2020","journal-title":"Diabetes"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/s41525-021-00178-9","article-title":"Genetic profiles of 103,106 individuals in the Taiwan Biobank provide insights into the health and history of Han Chinese","volume":"6","author":"Wei","year":"2021","journal-title":"NPJ Genom. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.trb.2022.05.007","article-title":"Spatially correlated nested logit model for spatial location choice","volume":"161","author":"Novales","year":"2022","journal-title":"Transp. Res. Part B Methodol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.1002\/hep.26009","article-title":"Genetic and functional identification of the likely causative variant for cholesterol gallstone disease at the ABCG5\/8 lithogenic locus","volume":"57","author":"Buch","year":"2013","journal-title":"Hepatology"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Liang, K.W., Huang, H.H., Wang, L., Lu, W.Y., Chou, Y.H., Tantoh, D.M., Nfor, O.N., Chiu, N.Y., Tyan, Y.S., and Liaw, Y.P. (2021). Risk of gallstones based on ABCG8 rs11887534 single nucleotide polymorphism among Taiwanese men and women. BMC Gastroenterol., 21.","DOI":"10.1186\/s12876-021-02060-5"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"639","DOI":"10.5551\/jat.62773","article-title":"Genetic Analysis in a Taiwanese Cohort of 750 Index Patients with Clinically Diagnosed Familial Hypercholesterolemia","volume":"29","author":"Huang","year":"2022","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s12944-021-01619-1","article-title":"Features of chinese patients with sitosterolemia","volume":"21","author":"Zhou","year":"2022","journal-title":"Lipids Health Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1373\/clinchem.2014.231365","article-title":"Refinement of variant selection for the LDL cholesterol genetic risk score in the diagnosis of the polygenic form of clinical familial hypercholesterolemia and replication in samples from 6 countries","volume":"61","author":"Futema","year":"2015","journal-title":"Clin. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1016\/j.jacl.2017.09.005","article-title":"ABCG5\/G8 gene is associated with hypercholesterolemias without mutation in candidate genes and noncholesterol sterols","volume":"11","author":"Bea","year":"2017","journal-title":"J. Clin. Lipidol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.jacl.2020.01.007","article-title":"ABCG5 and ABCG8 genetic variants in familial hypercholesterolemia","volume":"14","author":"Reeskamp","year":"2020","journal-title":"J. Clin. Lipidol."},{"key":"ref_55","first-page":"1917","article-title":"Rare and Deleterious Mutations in ABCG5\/ABCG8 Genes Contribute to Mimicking and Worsening of Familial Hypercholesterolemia Phenotype","volume":"83","author":"Tada","year":"2019","journal-title":"Circ. J. Off. J. Jpn. Circ. Soc."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1161\/CIRCGENETICS.109.907873","article-title":"Genetic regulation of serum phytosterol levels and risk of coronary artery disease","volume":"3","author":"Teupser","year":"2010","journal-title":"Circulation. Cardiovasc. Genet."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s12944-019-1183-4","article-title":"Beneficial effect of ezetimibe-atorvastatin combination therapy in patients with a mutation in ABCG5 or ABCG8 gene","volume":"19","author":"Tada","year":"2020","journal-title":"Lipids Health Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/j.bpg.2006.05.004","article-title":"Gallstone disease: Epidemiology of gallbladder stone disease","volume":"20","author":"Shaffer","year":"2006","journal-title":"Best Pract. Res. Clin. Gastroenterol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e12935","DOI":"10.1111\/eci.12935","article-title":"Genetics of gallstone disease","volume":"48","author":"Rebholz","year":"2018","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_60","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_61","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1111\/j.1365-2796.2010.02249.x","article-title":"Gallstone disease in Swedish twins: Risk is associated with ABCG8 D19H genotype","volume":"268","author":"Katsika","year":"2010","journal-title":"J. Intern. Med."},{"key":"ref_62","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_63","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1053\/j.gastro.2016.04.007","article-title":"Four Susceptibility Loci for Gallstone Disease Identified in a Meta-analysis of Genome-Wide Association Studies","volume":"151","author":"Joshi","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1111\/j.1478-3231.2008.01907.x","article-title":"Single nucleotide polymorphism in the ABCG8 transporter gene is associated with gallbladder cancer susceptibility","volume":"29","author":"Srivastava","year":"2009","journal-title":"Liver Int. Off. J. Int. Assoc. Study Liver"},{"key":"ref_65","first-page":"1585","article-title":"Common variant p.D19H of the hepatobiliary sterol transporter ABCG8 increases the risk of gallstones in children","volume":"42","author":"Krawczyk","year":"2022","journal-title":"Liver Int. Off. J. Int. Assoc. Study Liver"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Jiang, Z.Y., Cai, Q., and Chen, E.Z. (2014). Association of three common single nucleotide polymorphisms of ATP binding cassette G8 gene with gallstone disease: A meta-analysis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087200"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Renner, O., L\u00fctjohann, D., Richter, D., Strohmeyer, A., Schimmel, S., M\u00fcller, O., Stange, E.F., and Harsch, S. (2013). Role of the ABCG8 19H risk allele in cholesterol absorption and gallstone disease. BMC Gastroenterol., 13.","DOI":"10.1186\/1471-230X-13-30"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/ejhg.2015.63","article-title":"Lipids, obesity and gallbladder disease in women: Insights from genetic studies using the cardiovascular gene-centric 50K SNP array","volume":"24","author":"Rodriguez","year":"2016","journal-title":"Eur. J. Hum. Genet. EJHG"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1038\/ki.2012.252","article-title":"Plekhh2, a novel podocyte protein downregulated in human focal segmental glomerulosclerosis, is involved in matrix adhesion and actin dynamics","volume":"82","author":"Perisic","year":"2012","journal-title":"Kidney Int."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1038\/s41419-022-05307-5","article-title":"PLEKHH2 binds \u03b2-arrestin1 through its FERM domain, activates FAK\/PI3K\/AKT phosphorylation, and promotes the malignant phenotype of non-small cell lung cancer","volume":"13","author":"Wang","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1007\/s00439-008-0548-y","article-title":"Sequence variants in the PLEKHH2 region are associated with diabetic nephropathy in the GoKinD study population","volume":"124","author":"Greene","year":"2008","journal-title":"Hum. Genet."},{"key":"ref_72","first-page":"106","article-title":"Genome-wide association study identifies pharmacogenomic loci linked with specific antihypertensive drug treatment and new-onset diabetes","volume":"18","author":"Chang","year":"2018","journal-title":"Pharm. J."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Cunha, M.L.R., Meijers, J.C.M., Rosendaal, F.R., Vlieg, A.V.H., Reitsma, P.H., and Middeldorp, S. (2017). Whole exome sequencing in thrombophilic pedigrees to identify genetic risk factors for venous thromboembolism. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0187699"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1161\/CIRCRESAHA.117.312086","article-title":"Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease","volume":"122","author":"Verweij","year":"2018","journal-title":"Circ. Res."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Abdullah, M.M.H., Vazquez-Vidal, I., Baer, D.J., House, J.D., Jones, P.J.H., and Desmarchelier, C. (2021). Common Genetic Variations Involved in the Inter-Individual Variability of Circulating Cholesterol Concentrations in Response to Diets: A Narrative Review of Recent Evidence. Nutrients, 13.","DOI":"10.3390\/nu13020695"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/3\/754\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:59:38Z","timestamp":1760122778000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/3\/754"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,20]]},"references-count":75,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["genes14030754"],"URL":"https:\/\/doi.org\/10.3390\/genes14030754","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,20]]}}}