Functional polymorphism of human glutathione transferase A2

Natasha Tetlow, Philip G. Board*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    27 Citations (Scopus)

    Abstract

    Objectives: Single nucleotide polymorphisms that cause amino acid substitutions in enzymes involved in the metabolism of xenobiotics can potentially have a significant effect on the efficacy and safety of therapeutic drugs. Methods: We have utilized a bioinformatic approach to identify new polymorphisms in the glutathione transferase super family. Results and conclusions: In this report we describe a P110S polymorphism in GSTA2 that occurs at a low frequency in Africans, Chinese and Europeans. The serine containing isoform has significantly diminished activity with a range of substrates including, Δ5-Androsten-3,17-dione, 1 -chloro-2,4-dinitrobenzene and cumene hydroperoxide. The activity with cumene hydroperoxide may reflect a diminished physiological function since the glutathione peroxidase activity of GSTA2-2 plays a role in prostaglandin synthesis. In contrast, activity with p-nitrophenol acetate was significantly elevated. The position of this polymorphism in the active site and its effects on model substrates suggest that further investigation of its capacity to conjugate alkylating drugs is warranted.

    Original languageEnglish
    Pages (from-to)111-116
    Number of pages6
    JournalPharmacogenetics
    Volume14
    Issue number2
    DOIs
    Publication statusPublished - Feb 2004

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