ArticleJournal of the Chinese Medical Association : JCMA2021
The association of transporter ABCC2 (MRP2) genetic variation and drug-induced hyperbilirubinemia.
Article in Journal of the Chinese Medical Association : JCMA, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed, 16 citations in OpenAlex.
- Metabolomics and Machine Learning Uncover 5'-Methylthioadenosine as a Metabolic Indicator of Mixed-Pattern Drug-Induced Liver Injury.Metabolites · 2026Article
- Risk Assessment for Drug-Induced Hyperbilirubinemia: A Mechanistic Approach.CPT: pharmacometrics & systems pharmacology · 2026Article
- Structural basis for the transport and regulation mechanism of the multidrug resistance-associated protein 2.Nature communications · 2025Article
- ABCC2 p.R393W variant contributes to Dubin-Johnson syndrome by targeting MRP2 to proteasome degradation.eGastroenterology · 2024Article
- Molecular and Clinical Links between Drug-Induced Cholestasis and Familial Intrahepatic Cholestasis.International journal of molecular sciences · 2023Review
- Role and Regulation of Hepatobiliary ATP-Binding Cassette Transporters during Chemical-Induced Liver Injury.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- Article
- Clinical characteristics and outcomes of drug-induced liver injury in Taiwan: With emphasis on the impact of chronic hepatitis B infection.Journal of the Chinese Medical Association : JCMA · 2022Article
- Association ofFrontiers in pharmacology · 2022Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHyperbilirubinemia is a predictor of severe drug-induced liver injury (DILI). Hepatobiliary ATP-binding cassette (ABC) transporters play an important role in the transportation of many drugs and bilirubin; however, little is known about these transporters and the risk of DILI. The aim of this study was to explore associations between genetic variations in important ABC transporters and susceptibility to DILI, with a particular focus on hyperbilirubinemia.
methodsA total of 200 patients with DILI and 200 healthy controls were enrolled as the training dataset. Another 106 patients with DILI were recruited as the validation dataset. They were genotyped for ABCB11 (BSEP) rs2287622, ABCB1 (MDR1) rs1128503, rs1045642, ABCB4 (MDR3) rs2230028, ABCC2 (MRP2) rs1885301, rs717620, rs2273697, rs3740066 and rs8187710 using polymerase chain reaction-based TaqMan genotyping assays.
resultsThere were no statistical differences in any of the nine ABC transporter single nucleotide polymorphisms between the DILI and control groups. However, in the DILI group, the patients with hyperbilirubinemia had a higher frequency of the ABCC2 rs717620 C/T and T/T genotypes than those without hyperbilirubinemia (44.2% vs 20.2%, p = 0.001). After adjusting for other confounding factors, the ABCC2 rs717620 T variant was still associated with an increased risk of hyperbilirubinemia (adjusted odds ratio [OR]: 3.83, 95% confidence interval [CI]: 1.73-8.48, p = 0.001). This association was confirmed by the validation dataset (adjusted OR: 3.92, 95% CI: 1.42-10.81, p = 0.015). We also found that the mortality group had higher frequencies of the ABCC2 (MRP2) rs717620 C/T and T/T genotypes than the survival group (50.0% vs 27.9%, p = 0.048).
conclusionCarriage of the ABCC2 (MRP2) rs717620 T variant may increase the risk of hyperbilirubinemia and mortality in patients with DILI. Screening for this variant may help to prevent and mitigate drug-induced hyperbilirubinemia.
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