The role of CYP and UGT polymorphisms in the biotransformation of phthalates and DINCH were investigated in Slovenian men and lactating women.
In the human body, phthalates and DINCH undergo biotransformation, which involves the oxidation of the monoester side chain by cytochrome P450 enzymes (CYPs) in the first phase and conjugation mostly by UDP-glucuronyl transferases (UGTs) in the second phase. This results in the excretion of various primary and secondary metabolites mostly via urine. Various studies observed inter-individual variability in the patterns of those urine metabolites. Genetic variations in CYP and UGT genes were proposed, but not yet studied, as one of the possible contributors to this variability.
Therefore, in our study we investigated, for the first time, the possible influence of single nucleotide polymorphisms (SNPs) in three CYP (CYP2C9, CYP2C19, CYP2D) and two UGT (UGT2B15 and UGT1A7) genes on the biotransformation of phthalates and DINCH using human biomonitoring data on 274 men and 289 lactating women from Slovenia.
Our results confirm the previously only in vitro observed influence of CYP2C9 rs1799853 and rs1057910 SNPs on the reduced biotransformation of DEHP and suggest a negative influence of rs1057910 SNP on DINCH biotransformation. Moreover, CYP2C19 rs12248560 SNP was associated with a higher excretion of secondary metabolites of DEHP, DiNP and DiDP while the UGT1A7 rs11692021 SNP resulted in higher urinary levels of BBzP, DiBP and DINCH metabolites.
Although most of the variability in urinary levels of phthalates and DINCH metabolites remains unexplained, we demonstrate that the above-mentioned SNPs could represent important biomarkers of susceptibility to phthalates and DINCH exposure that have been so far unrecognised.
This study is presented in a manuscript: “Assessment of susceptibility to phthalate and DINCH exposure through CYP and UGT single nucleotide polymorphisms” prepared by Stajnko A. Runkel A.A., Kosjek T., Snoj Tratnik J., Mazej D. Falnoga I., Horvat M., and published in Environmental International, 2022 and is available online: https://doi.org/10.1016/j.envint.2021.107046