AIM: Estimating polymorphic allele frequencies of the NADPH-CYP450 oxidoreductase (POR) gene in a Czech Slavic population. METHODS: The POR gene was analyzed in 322 individuals from a control cohort by sequencing and high resolution melting analysis. RESULTS: We identified seven unreported SNP genetic variations, including two SNPs in the 5' flanking region (g.4965C>T and g.4994G>T), one intronic variant (c.1899-20C>T), one synonymous SNP (p.20Ala=) and three nonsynonymous SNPs (p.Thr29Ser, p.Pro384Leu and p.Thr529Met). The p.Pro384Leu variant exhibited reduced enzymatic activities compared with wild-type. CONCLUSION: New POR variant identification indicates the number of uncommon variants might be specific for each subpopulation being investigated, particularly germane to the singular role that POR plays in providing reducing equivalents to all CYP450s in the endoplasmic reticulum. Original submitted 15 September 2014; Revision submitted 17 November 2014.

• Klíčová slova
• CYP, Czech Slavic population, NADPH-cytochrome, P450 oxidoreductase, P450 reductase, POR, allele frequencies, haplotype, pharmacogenetics,
• MeSH
• DNA genetika   MeSH
• dospělí MeSH
• frekvence genu MeSH
• genetická variace MeSH
• haplotypy MeSH
• jednonukleotidový polymorfismus * MeSH
• kinetika MeSH
• kohortové studie MeSH
• konformace proteinů MeSH
• lidé MeSH
• missense mutace MeSH
• molekulární modely MeSH
• novorozenec MeSH
• sekvence nukleotidů MeSH
• substituce aminokyselin MeSH
• systém (enzymů) cytochromů P-450 chemie   genetika   metabolismus   MeSH
• vazebná nerovnováha MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• DNA MeSH
• POR protein, human MeSH Prohlížeč
• systém (enzymů) cytochromů P-450 MeSH

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.

• MeSH
• farmakogenetika MeSH
• frekvence genu MeSH
• genetické markery MeSH
• haplotypy MeSH
• jednonukleotidový polymorfismus * MeSH
• lidé MeSH
• missense mutace * MeSH
• molekulární modely MeSH
• NADPH-cytochrom c-reduktasa chemie   genetika   MeSH
• sekvenční analýza DNA MeSH
• vazebná nerovnováha MeSH
• Židé genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Geografické názvy
• Izrael epidemiologie   MeSH
• Maroko etnologie   MeSH
• Názvy látek
• genetické markery MeSH
• NADPH-cytochrom c-reduktasa MeSH