Research Progress on the Application of Cytochrome P450 Gene Polymorphisms in Toxicological Analysis

doi:10.3969/j.issn.1671-2072.2025.04.005

Abstract

Abstract: With remarkable advances in high-throughput sequencing technology and molecular genetics, research on the genetic mechanisms of drug (toxicant) metabolism have made a leap from single chemical assay to systematic molecular analysis in forensic medicine. The discipline has systematically revealed the effects of toxicant exposure on gene expression regulation, epigenetic modifications, and metabolite abnormalities by integrating genomics, epigenetics, and toxicology. Based on cytochrome P450 (CYP450) gene polymorphisms, this review analyses the differences in sensitivity to the same drug in different individuals and explores the mechanisms that lead to toxicity through abnormal drug metabolism. It further investigates genotypes and allelic variants of genes encoding drug metabolising enzymes to assess risks associated with exposure to chemicals, drugs, and environmental pollutants. Artificial intelligence (AI) machine learning is employed to predict and identify genotypes of various compounds as well as metabolites, enabling in vivo or in vitro gene expression modelling analysis for enhanced accuracy of genotype prediction. By shifting the focus from qualitative toxicant analysis to toxicodynamic mechanisms, this study provides critical insights for determining the cause and manner of death in drug abuse or poisoning-related fatalities. As a detection tool, CYP450 gene polymorphisms are reshaping forensic toxicological identification paradigms, serving as a core driver propelling forensic science into the “molecular era”.

Key words: cytochrome P450 (CYP450), gene polymorphism, forensic medicine, artificial intelligence (AI)

摘要： 随着高通量测序技术与分子遗传学的显著进展，药（毒）物代谢的遗传机制在法医学领域实现了从单一化学检测到系统性分子解析的跨越式升级。通过整合基因组学、表观遗传学与毒理学的相关研究，系统性揭示了毒物暴露对基因表达调控、表观遗传修饰和代谢产物异常的影响。基于细胞色素P450（cytochrome P450，CYP450）基因多态性，分析不同个体对同一药物的敏感性差异，探讨其通过药物代谢异常导致中毒的机制。研究和分析药物代谢酶编码基因的基因型和等位基因变异，评估机体暴露于化学品、药物和环境污染物有关的风险。利用人工智能机器学习来预测和识别各种化合物以及代谢物的基因型，实现体内或体外基因表达模型分析，以提高基因表型预测的准确性。通过从毒物定性分析转向毒效动力学机制研究，为药物滥用或死亡案件的死亡原因分析和死亡方式推断提供线索。CYP450基因多态性作为一种检测手段，正在重塑法医学毒理鉴定模式，成为法医科学进入“分子时代”的核心驱动力。

关键词: 细胞色素P450, 基因多态性, 法医学, 人工智能

CLC Number:

DF795.1

CHENG Zhongping, JIA Zelei, XU Xingmin, MO Yaonan. Research Progress on the Application of Cytochrome P450 Gene Polymorphisms in Toxicological Analysis[J]. Chinese Journal of Forensic Sciences, 2025(4): 55-62.

程忠平, 贾泽雷, 徐兴敏, 莫耀南. 细胞色素P450基因多态性在毒物分析中的应用研究进展[J]. 中国司法鉴定, 2025(4): 55-62.

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