ArticlePloS one2015
The Role of ARF6 in Biliary Atresia.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 66 citations in OpenAlex.
- Immune and genetic landscapes of biliary atresia: a pathway to precision medicine.BMC pediatrics · 2025Article
- Amyloid precursor protein as a fibrosis marker in infants with biliary atresia.Pediatric research · 2025Article
- Organoids in biliary atresia.World journal of pediatric surgery · 2025Review
- Heritable Chronic Cholestatic Liver Diseases: A Review.Journal of clinical and translational hepatology · 2024Review
- Biliary atresia.Nature reviews. Disease primers · 2024Review
- Biliary atresia is associated with polygenic susceptibility in ciliogenesis and planar polarity effector genes.Journal of hepatology · 2023Article
- The association of immune-related genes and the potential role of IL10 with biliary atresia.Pediatric research · 2023Article
- Contribution ofInternational journal of molecular sciences · 2023Article
- Genetic Contributions to Biliary Atresia: A Developmental Cholangiopathy.Seminars in liver disease · 2023Review
- Association analysis and functional follow-up identified common variants ofFrontiers in genetics · 2023Article
- Biliary Atresia Animal Models: Is the Needle in a Haystack?International journal of molecular sciences · 2022Review
- Current Understanding in the Clinical Characteristics and Molecular Mechanisms in Different Subtypes of Biliary Atresia.International journal of molecular sciences · 2022Review
- Biliary Atresia: A Complex Hepatobiliary Disease with Variable Gene Involvement, Diagnostic Procedures, and Prognosis.Diagnostics (Basel, Switzerland) · 2022Review
- Genetic Factors and Their Role in the Pathogenesis of Biliary Atresia.Frontiers in pediatrics · 2022Review
- A joint transcriptional regulatory network and protein activity inference analysis identifies clinically associated master regulators for biliary atresia.Frontiers in pediatrics · 2022Article
- Biliary Atresia - emerging diagnostic and therapy opportunities.EBioMedicine · 2021Review
- Microtissue Geometry and Cell-Generated Forces Drive Patterning of Liver Progenitor Cell Differentiation in 3D.Advanced healthcare materials · 2021Article
- Xmrks the Spot: Fish Models for Investigating Epidermal Growth Factor Receptor Signaling in Cancer Research.Cells · 2021Review
- RNA Splicing: A Versatile Regulatory Mechanism in Pediatric Liver Diseases.Frontiers in molecular biosciences · 2021Review
- Congenital biliary atresia is correlated with disrupted cell junctions and polarity caused by Cdc42 insufficiency in the liver.Theranostics · 2021Article
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Authors and funding
20 authors at 8 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsAltered extrahepatic bile ducts, gut, and cardiovascular anomalies constitute the variable phenotype of biliary atresia (BA).
methodsTo identify potential susceptibility loci, Caucasian children, normal (controls) and with BA (cases) at two US centers were compared at >550000 SNP loci. Systems biology analysis was carried out on the data. In order to validate a key gene identified in the analysis, biliary morphogenesis was evaluated in 2-5-day post-fertilization zebrafish embryos after morpholino-antisense oligonucleotide knockdown of the candidate gene ADP ribosylation factor-6 (ARF6, Mo-arf6).
resultsAmong 39 and 24 cases at centers 1 and 2, respectively, and 1907 controls, which clustered together on principal component analysis, the SNPs rs3126184 and rs10140366 in a 3' flanking enhancer region for ARF6 demonstrated higher minor allele frequencies (MAF) in each cohort, and 63 combined cases, compared with controls (0.286 vs. 0.131, P = 5.94x10-7, OR 2.66; 0.286 vs. 0.13, P = 5.57x10-7, OR 2.66). Significance was enhanced in 77 total cases, which included 14 additional BA genotyped at rs3126184 only (p = 1.58x10-2, OR = 2.66). Pathway analysis of the 1000 top-ranked SNPs in CHP cases revealed enrichment of genes for EGF regulators (p<1 x10-7), ERK/MAPK and CREB canonical pathways (p<1 x10-34), and functional networks for cellular development and proliferation (p<1 x10-45), further supporting the role of EGFR-ARF6 signaling in BA. In zebrafish embryos, Mo-arf6 injection resulted in a sparse intrahepatic biliary network, several biliary epithelial cell defects, and poor bile excretion to the gall bladder compared with uninjected embryos. Biliary defects were reproduced with the EGFR-blocker AG1478 alone or with Mo-arf6 at lower doses of each agent and rescued with arf6 mRNA.
conclusionsThe BA-associated SNPs identify a chromosome 14q21.3 susceptibility locus encompassing the ARF6 gene. arf6 knockdown in zebrafish implicates early biliary dysgenesis as a basis for BA, and also suggests a role for EGFR signaling in BA pathogenesis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.