Related Experiment Videos
ABCB1 rs2032582 as a Potential Biomarker for Predicting Scutellaria baicalensis Georgi-Drug Induced Liver Injury in
Lihong Fu1, Longshan Ji1, Xiaji Yan1
1Department of Hepatopathy, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China; Laboratory of Cellular Immunity, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Ethnopharmacological Relevance:
Scutellaria baicalensis Georgi (SBG, Huangqin), a prominent traditional Chinese medicine, has a long history of clinical use for clearing heat and detoxifying, a classic TCM therapeutic concept corresponding to its well-documented anti-inflammatory, antimicrobial and hepatoprotective activities in modern pharmacological research. Despite its widespread therapeutic benefits, growing clinical evidence has linked SBG and its preparations with herb-induced liver injury (HILI). However, the population-level incidence of SBG-related drug-induced liver injury (SBG-DILI) and the potential genetic susceptibility mechanisms remain poorly understood.
Objective:
To determine the clinical incidence of SBG-DILI, characterize its dose-dependent toxicity pattern, and identify candidate pharmacogenomic biomarkers of genetic susceptibility (specifically ABCB1 polymorphisms) in the Chinese Han population.
Methods:
We conducted two multicenter studies across four Grade A tertiary hospitals of traditional Chinese medicine in Shanghai (the highest-tier public medical institutions in China), integrating a large-scale retrospective cohort and a two-phase prospective genetic association analysis. In the retrospective study, 1,928,526 outpatients were screened, and the patients of SBG-DILI were enrolled and then the relationships between SBG dosage, treatment duration and hepatotoxicity risk were analyzed. The prospective arm utilized an initial single-nucleotide polymorphism (SNP) discovery screening in 12 patients with rechallenge-proven SBG-DILI, followed by independent targeted genotyping validation via the MassArray iPLEX system in a replication cohort (20 SBG-DILI cases, 25 other-DILI cases, and 60 matched population controls).
Results:
All cases of liver injury were verified using causality assessment method (RUCAM score >6 and iEC-based HILI criteria) ; the confirmed clinical incidence of SBG-DILI was 0.095% (72/75,564). Multivariate logistic regression confirmed a clear dose-toxicity relationship, where daily doses exceeding the pharmacopoeia recommendation (>10 g/day) significantly increased the risk of liver injury (adjusted OR = 2.210, 95% CI = 1.185-4.122, P = 0.013). Genetically, the non-synonymous mutation ABCB1 rs2032582 (C allele) was identified as a strong, independent genetic risk factor. The homozygote C/C genotype was remarkably overrepresented in SBG-DILI patients (58.3%) compared to other-DILI cases (4.5%) and population controls (16.3%). Under the log-additive model, the C allele substantially augmented susceptibility to SBG-DILI (adjusted OR = 8.30 vs. other-DILI, P = 0.0001; adjusted OR = 3.70 vs. controls, P = 0.0017).
Conclusion:
SBG-DILI, characterized by distinct dose-dependency, is relatively infrequent, but clinically important valvular problems may arises. The ABCB1 rs2032582 variant represents a pivotal genetic susceptibility locus in the Chinese Han population. These findings provide compelling evidence for predicting toxicity of herbal medicine and suggest that genotype-assisted risk stratification could facilitate safer, more precise applications of traditional herbal remedies.
