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

Mria Tomkov, Christopher C. Marohnic, David Gurwitz, Ondaej Eda, Bettie Sue Siler Masters, Pavel Martsek

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 201.

Original languageEnglish (US)
Pages (from-to)543-554
Number of pages12
JournalPharmacogenomics
Volume13
Issue number5
DOIs
StatePublished - Apr 2012

Fingerprint

Oxidoreductases
Population
Single Nucleotide Polymorphism
Jews
Pharmacogenetics
NADP
Cytochrome P-450 Enzyme System
Open Reading Frames
Biomarkers
Alleles
Tissue Donors
Electrons
Pharmaceutical Preparations
Genes

Keywords

  • allele frequencies
  • CYP oxidoreductase
  • haplotype
  • Jewish populations
  • pharmacogenetics
  • POR

ASJC Scopus subject areas

  • Pharmacology
  • Genetics
  • Molecular Medicine

Cite this

Tomkov, M., Marohnic, C. C., Gurwitz, D., Eda, O., Masters, B. S. S., & Martsek, P. (2012). Identification of six novel P450 oxidoreductase missense variants in Ashkenazi and Moroccan Jewish populations. Pharmacogenomics, 13(5), 543-554. https://doi.org/10.2217/pgs.12.21

Identification of six novel P450 oxidoreductase missense variants in Ashkenazi and Moroccan Jewish populations. / Tomkov, Mria; Marohnic, Christopher C.; Gurwitz, David; Eda, Ondaej; Masters, Bettie Sue Siler; Martsek, Pavel.

In: Pharmacogenomics, Vol. 13, No. 5, 04.2012, p. 543-554.

Research output: Contribution to journalArticle

Tomkov, M, Marohnic, CC, Gurwitz, D, Eda, O, Masters, BSS & Martsek, P 2012, 'Identification of six novel P450 oxidoreductase missense variants in Ashkenazi and Moroccan Jewish populations', Pharmacogenomics, vol. 13, no. 5, pp. 543-554. https://doi.org/10.2217/pgs.12.21
Tomkov, Mria ; Marohnic, Christopher C. ; Gurwitz, David ; Eda, Ondaej ; Masters, Bettie Sue Siler ; Martsek, Pavel. / Identification of six novel P450 oxidoreductase missense variants in Ashkenazi and Moroccan Jewish populations. In: Pharmacogenomics. 2012 ; Vol. 13, No. 5. pp. 543-554.
@article{3786e20cdaa9416fb597a3f70e19a32c,
title = "Identification of six novel P450 oxidoreductase missense variants in Ashkenazi and Moroccan Jewish populations",
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 201.",
keywords = "allele frequencies, CYP oxidoreductase, haplotype, Jewish populations, pharmacogenetics, POR",
author = "Mria Tomkov and Marohnic, {Christopher C.} and David Gurwitz and Ondaej Eda and Masters, {Bettie Sue Siler} and Pavel Martsek",
year = "2012",
month = "4",
doi = "10.2217/pgs.12.21",
language = "English (US)",
volume = "13",
pages = "543--554",
journal = "Pharmacogenomics",
issn = "1462-2416",
publisher = "Future Medicine Ltd.",
number = "5",

}

TY - JOUR

T1 - Identification of six novel P450 oxidoreductase missense variants in Ashkenazi and Moroccan Jewish populations

AU - Tomkov, Mria

AU - Marohnic, Christopher C.

AU - Gurwitz, David

AU - Eda, Ondaej

AU - Masters, Bettie Sue Siler

AU - Martsek, Pavel

PY - 2012/4

Y1 - 2012/4

N2 - 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 201.

AB - 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 201.

KW - allele frequencies

KW - CYP oxidoreductase

KW - haplotype

KW - Jewish populations

KW - pharmacogenetics

KW - POR

UR - http://www.scopus.com/inward/record.url?scp=84859251297&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859251297&partnerID=8YFLogxK

U2 - 10.2217/pgs.12.21

DO - 10.2217/pgs.12.21

M3 - Article

C2 - 22462747

AN - SCOPUS:84859251297

VL - 13

SP - 543

EP - 554

JO - Pharmacogenomics

JF - Pharmacogenomics

SN - 1462-2416

IS - 5

ER -