Correlation Between CYP1A2 Genetic Polymorphism and Drug Response

CYP1A2 is a key cytochrome P450 enzyme involved in the metabolism of various xenobiotics and endogenous compounds. This study investigated the genetic variability, functional annotation, and structural implications of CYP1A2 variants. We utilized the data from 2504 individuals across 26 populations from the 1000 Genomes Project Consortium Phase 3 release, and applied combinative bioinformatics, including genomics and molecular modeling approaches. The Gene Ontology (GO) enrichment analysis results indicated the CYP1A2 gene enrichment in biological processes related to toxin metabolism and oxidative reactions. Variants mapping analysis identified functional consequences within both regulatory and coding regions. The SNPs analysis identified three lead SNPs (rs2470890, rs17861157, rs11636419) showing potential regulatory roles. And SNP-to-gene mapping suggested interactions with genes such as CSK, CYP1A1, and CYP11A1, implying possible co-regulation or downstream effects. Finally, molecular docking experiments were performed on wild-type CYP1A2 and six key mutants bearing missense mutations located within 10 Å of the enzyme’s binding pocket. The docking results indicate potential pharmacokinetics consequences could be altered by different genetic mutations. This study broadens our understanding of CYP1A2 genetic variability and its significance in pharmacogenomics, and provides insights to the future personalized medicine.