The influence of genetic variants of CYP1A2 and CYP2A6 on the metabolism of lower-chlorinated polychlorinated biphenyls (PCBs) – relevance for occupational health prevention

Status:

ongoing

Aims:

The aim of the project is to investigate the influence of genetic variants of the enzymes CYP1A2 and CYP2A6 on the metabolism of lower-chlorinated polychlorinated biphenyls, particularly PCB 28, PCB 52 and PCB 101. The project focuses on whether functionally relevant gene polymorphisms affect the formation of toxicologically relevant hydroxylated PCB metabolites, individual elimination kinetics and the risk of PCB-associated health effects. The results are intended to support the identification of genetically vulnerable individuals after occupational PCB exposure and to improve occupational medical prevention, follow-up care and risk assessment.

Activities/Methods:

Archived blood cell samples from participants of the HELPcB cohort will be used for DNA extraction. Genotyping will be performed using TaqMan® SNP and CNV assays targeting functionally relevant variants in CYP1A2 and CYP2A6, including variants associated with reduced, increased or abolished enzyme function as well as copy number variants. The resulting genetic profiles will be linked to existing and, where necessary, newly generated data on hydroxylated PCB metabolites, PCB elimination half-lives and documented health outcomes, including skin cancer, depressive syndromes, other psychiatric disorders and thyroid diseases. Statistical analyses will include descriptive analyses, regression models, mixed models and analyses of gene-gene and gene-environment interactions, while accounting for relevant covariates such as age, sex, BMI, blood lipid levels and smoking status.

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