Two common single nucleotide polymorphisms in the gene encoding β-carotene 15,15′-monoxygenase alter β-carotene metabolism in female volunteers

Leung, W. C., Hessel, S., Meplan, C. , Flint, J., Oberhauser, V., Tourniaire, F., Hesketh, J. E., Von Lintig, J. and Lietz, G. (2009) Two common single nucleotide polymorphisms in the gene encoding β-carotene 15,15′-monoxygenase alter β-carotene metabolism in female volunteers. FASEB Journal, 23 (4). pp. 1041-1053. ISSN 0892-6638

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The key enzyme responsible for β-carotene conversion into retinal is β-carotene 15,15�-monoxygenase (BCMO1). Since it has been reported that the conversion of β-carotene into vitamin A is highly variable in up to 45 of healthy individuals, we hypothesized that genetic polymorphisms in the BCMO1 gene could contribute to the occurrence of the poor converter phenotype. Here we describe the screening of the total open reading frame of the BCMO1 coding region that led to the identification of two common nonsynonymous single nucleotide polymorphisms (R267S: rs12934922; A379V: rs7501331) with variant allele frequencies of 42 and 24, respectively. In vitro biochemical characterization of the recombinant 267S + 379V double mutant revealed a reduced catalytic activity of BCMO1 by 57 (P<0.001). Assessment of the responsiveness to a pharmacological dose of β-carotene in female volunteers confirmed that carriers of both the 379V and 267S + 379V variant alleles had a reduced ability to convert β-carotene, as indicated through reduced retinyl palmitate: β-carotene ratios in the triglyceride-rich lipoprotein fraction -32% (P=0.005) and -69% (P=0.001), respectively and increased fasting β-carotene concentrations +160% (P=0.025) and +240% (P=0.041), respectively. Our data show that there is genetic variability in β-carotene metabolism and may provide an explanation for the molecular basis of the poor converter phenotype within the population. © FASEB.

Additional Information:Published online before print December 22, 2008
Keywords:beta carotene, beta carotene 15,15' monooxygenase, lipoprotein, retinol palmitate, triacylglycerol, antioxidant, BCMO1 protein, human, recombinant protein, adult, article, catalysis, chemical analysis, concentration response, enzyme activity, female, gene frequency, gene identification, genetic code, genetic variability, heterozygote, human, human cell, human experiment, in vitro study, mutant, open reading frame, phenotype, priority journal, protein determination, screening, single nucleotide polymorphism, vitamin metabolism, vitamin supplementation, allele, genetics, metabolism, Alleles, Antioxidants, beta-Carotene 15,15'-Monooxygenase, Humans, Open Reading Frames, Polymorphism, Single Nucleotide, Recombinant Proteins, Young Adult
Subjects:B Subjects allied to Medicine > B100 Anatomy, Physiology and Pathology
Divisions:College of Science > School of Life Sciences
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ID Code:12460
Deposited On:10 Jan 2014 14:49

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