Research Article

Identification of six novel P450 oxidoreductase missense variants in Ashkenazi and Moroccan Jewish populations

Department of Pediatrics, 1st Faculty of Medicine, Charles University, 128 08 Prague, Czech Republic

Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA

Department of Human Molecular Genetics & Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel

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Ondřej Šeda

Institute of Biology & Medical Genetics, 1st Faculty of Medicine, Charles University, 128 08 Prague, Czech Republic

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Bettie Sue Siler Masters

Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA

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Pavel Martásek

* Author for correspondence

Department of Pediatrics, 1st Faculty of Medicine, Charles University, 128 08 Prague, Czech Republic.

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Email the corresponding author at pavel.martasek@gmail.com

Published Online:30 Mar 2012https://doi.org/10.2217/pgs.12.21

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Abstract

Background: The enzyme NADPH–P450 oxidoreductase (POR) is the main electron donor to all microsomal CYPs. The possible contribution of common POR variants to inter- and intra-individual variability in drug metabolism is of great pharmacogenetic interest. Aim: To search for POR polymorphic alleles and estimate their frequencies in a Jewish population. Materials & methods: We analyzed the POR gene in 301 Ashkenazi and Moroccan Jews. Results: A total of 30 POR SNPs were identified, nine in the noncoding regions and 21 in the protein-coding regions (ten synonymous, 11 missense). Six of these missense variants are previously undescribed (S102P, V164M, V191M, D344N, E398A and D648N). Conclusion: The data collected in this study on missense POR SNPs, interpreted in light of the crystallographic structure of human POR, indicate that some POR missense variants may be potential biomarkers for future POR pharmacogenetic screening.

Original submitted 28 September 2011; Revision submitted 9 February 2012

Keywords:

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

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Acknowledgements

The authors thank J-J Kim from Medical College of Wisconsin (WI, USA) for helpful discussions regarding potential structural consequences of mutations. The authors thank the anonymous donors of the NLGIP biobank at Tel Aviv University (Tel Aviv, Israel), whose altruism and trust in biomedical research have made this study possible.

Disclaimer

The authors had full access to the data and take responsibility for its integrity. All authors have read and agree with the manuscript as written.

Financial & competing interests disclosure

Supported by grant GACR P301/10/1426 from Czech Granting Agency and the US NIH GM81568 to BSS Masters, who is the Robert A Welch Distinguished Professor in Chemistry (AQ0012) at the University of Texas Health Science Center at San Antonio (TX, USA). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

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