ABCB4 gene mutation-associated cholelithiasis in adults
Open accessAbstract
Background & aims We recently put forward arguments in favor of ABCB4 gene (adenosine triphosphate-binding cassette, subfamily B, member 4) defects as a risk factor for symptomatic cholelithiasis in adults. In this study, we characterized ABCB4 gene mutations in a series of patients with symptomatic cholelithiasis to determine the genetic basis and the clinical phenotype of ABCB4 gene mutation-associated cholelithiasis.Methods We analyzed the entire ABCB4 gene coding sequences in a first group of 32 patients who had a clinical history compatible with the syndrome previously described, in a second group of 28 patients who presented with a classic gallstone disease that justified a cholecystectomy, and in a third group of 33 patients without a history of cholelithiasis.Results We identified both heterozygous and homozygous ABCB4 gene point mutations in 18 of 32 (56%) patients who presented with clinical criteria of the syndrome, whereas no mutation was detected in the 2 other groups of patients (P < 0.001). Three independent clinical features were strongly associated with point mutations: recurrence of symptoms after cholecystectomy (odds ratio, 8.5); intrahepatic hyperechoic foci, intrahepatic sludge, or microlithiasis (odds ratio, 6.1); and age <40 years at the onset of symptoms (odds ratio, 3.0). ABCB4 gene point mutations were detected exclusively in the patients who showed 2 or 3 of these clinical features.Conclusions Our results show that ABCB4 gene mutations represent a major genetic risk factor in a symptomatic and recurring form of cholelithiasis in young adults.
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ABCB4 deficiency is associated with low phospholipid-associated cholelithiasis syndrome, intrahepatic cholestasis of pregnancy, oral contraceptive-induced cholestasis, small duct sclerosing cholangitis, and persistent hepatocellular secretory failure.
“ABCB4 deficiency has been associated with low phospholipid-associated cholelithiasis syndrome, intrahepatic cholestasis of pregnancy, oral contraceptive-induced cholestasis, small duct sclerosing cholangitis, and persistent hepatocellular secretory failure.282,283”
From EASL Clinical Practice Guidelines on sclerosing cholangitis (2022) · cites this paper as [283]
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- Authors
- Rosmorduc, O., Hermelin, B., Boelle, P., Parc, R., Taboury, J., & Poupon, R.
- Affiliations
- Inserm (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Corresponding author
- Poupon, Raoul
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2003-08
- Volume
- 125
- Issue
- 2
- Pages
- 452-459
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W2037661591
- Cited by
- 282
- References
- 38
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 8 · 2023: 11 · 2022: 13 · 2021: 8 · 2020: 8 · 2019: 14 · 2018: 10 · 2017: 11 · 2016: 7 · 2015: 6 · 2014: 11 · 2013: 16 · 2012: 10
- FWCI
- 7.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Institut National de la Santé et de la Recherche Médicale
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Gallbladder and Bile Duct Disorders
- Health Sciences › Medicine › Surgery › Pediatric Hepatobiliary Diseases and Treatments
- Keywords
- ABCB4 gene, gallstones, gallstone disease, genetic risk factors, young adults
- MeSH terms
- Adult, Aged, Cholelithiasis, Cholesterol, Female, Humans, Liver Diseases, Male, Middle Aged, Mutation, Phenotype, Phospholipids, Polymorphism, Genetic, Risk Factors, ATP Binding Cassette Transporter, Subfamily B, ATP-Binding Cassette Transporters
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