Genetic polymorphisms in cytochrome P450 oxidoreductase influence microsomal P450-catalyzed drug metabolism

@article{Hart2008GeneticPI,
  title={Genetic polymorphisms in cytochrome P450 oxidoreductase influence microsomal P450-catalyzed drug metabolism},
  author={Steven N. Hart and Shuang Wang and Kaori Nakamoto and Chris Wesselman and Ye Li and Xiao-bo Zhong},
  journal={Pharmacogenetics and Genomics},
  year={2008},
  volume={18},
  pages={11-24}
}
Objectives Cytochrome P450 oxidoreductase (POR) is the only flavoprotein that donates electrons to all microsomal P450 enzymes, which catalyze the biosynthesis of steroids, fatty acids, and bile acids, as well as metabolism of more than 80% of prescription drugs. Although mutations in POR have been identified in several disease states with disordered steroidogenesis, effects of polymorphisms on drug metabolism in the general population are unclear. In this report, we performed a comprehensive… 
Polymorphisms in cytochrome P450 oxidoreductase and its effect on drug metabolism and efficacy
TLDR
Recent research on the effects of POR genetic polymorphisms on drug metabolism and therapy has been summarized and discussed, which can contribute to the rational use of drugs in clinic and the development of personalized medicine.
P450 oxidoreductase: genetic polymorphisms and implications for drug metabolism and toxicity
TLDR
POR is a polymorphic enzyme that can affect CYP-mediated drug metabolism as well as direct bioactivation of prodrugs and may help to explain altered drug-metabolizing phenotypes.
Pharmacogenomics of human liver cytochrome P450 oxidoreductase: multifactorial analysis and impact on microsomal drug oxidation.
TLDR
Investigating genetic and nongenetic POR variability and its impact on drug-oxidation activities in human liver microsomes provides a basis for further studies towards inclusion of POR polymorphisms in pharmacogenomic strategies.
Pharmacogenomics of human P450 oxidoreductase
TLDR
The work on variations in POR related to metabolism of drugs and xenobiotics and some trends are emerging that establish certain founder mutations in distinct populations, with Japanese, Caucasian, and Turkish populations showing repeated findings of similar mutations.
P450 Oxidoreductase deficiency: Analysis of mutations and polymorphisms
Pharmacogenetics of P450 oxidoreductase: effect of sequence variants on activities of CYP1A2 and CYP2C19
TLDR
The activity of individual POR mutants may vary greatly depending on the electron recipient used to assay activity, and the activity of a POR mutant to support catalysis by a particular P450 enzyme cannot be predicted by theactivity of that P OR mutant in an assay with a different P450 or with cytochrome c.
Pharmacogenetics of P450 oxidoreductase: implications in drug metabolism and therapy
TLDR
The effect of Por and its genetic polymorphisms on drug metabolism and therapy, as well as the potential mechanisms of POR pharmacogenetics are discussed.
Identification of Cytochrome P450 Oxidoreductase Gene Variants That Are Significantly Associated with the Interindividual Variations in Warfarin Maintenance Dose
TLDR
Results indicate, for the first time, that three common SNPs in the POR gene may contribute to the interindividual variability in warfarin maintenance dose.
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