Two common single nucleotide polymorphisms in the gene encoding beta-carotene 15,15'-monoxygenase alter beta-carotene metabolism in female volunteers.

Leung WC; Hessel S; Meplan CFlint JOberhauser VTourniaire FHesketh JEvon-Lintig JLietz G

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Two common single nucleotide polymorphisms in the gene encoding beta-carotene 15,15'-monoxygenase alter beta-carotene metabolism in female volunteers.

机译：Two common single nucleotide polymorphisms in the gene encoding beta-carotene 15,15'-monoxygenase alter beta-carotene metabolism in female volunteers.

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The key enzyme responsible for beta-carotene conversion into retinal is beta-carotene 15,15'-monoxygenase (BCMO1). Since it has been reported that the conversion of beta-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 beta-carotene in female volunteers confirmed that carriers of both the 379V and 267S + 379V variant alleles had a reduced ability to convert beta-carotene, as indicated through reduced retinyl palmitate:beta-carotene ratios in the triglyceride-rich lipoprotein fraction -32 (P=0.005) and -69 (P=0.001), respectively and increased fasting beta-carotene concentrations +160 (P=0.025) and +240 (P=0.041), respectively. Our data show that there is genetic variability in beta-carotene metabolism and may provide an explanation for the molecular basis of the poor converter phenotype within the population.

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《The FASEB Journal》 |2009年第4期|1041-1053|共13页
作者
Leung WC; Hessel S; Meplan CFlint JOberhauser VTourniaire FHesketh JEvon-Lintig JLietz G;
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Human Nutrition Research Centre, Newcastle University, Newcastle upon Tyne, UK.;

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正文语种英语
中图分类生物化学;
关键词
beta Carotene; Unmarried; Nucleotides; metabolic aspects; 核苷酸类;

Two common single nucleotide polymorphisms in the gene encoding beta-carotene 15,15'-monoxygenase alter beta-carotene metabolism in female volunteers.

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