Two common single nucleotide polymorphisms in the gene encoding β-carotene 15,15′-monoxygenase alter β-carotene metabolism in female volunteers
Two common single nucleotide polymorphisms in the gene encoding β-carotene 15,15′-monoxygenase alter β-carotene metabolism in female volunteers
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DOI：
10.1096/fj.08-121962
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发表时间：
2009-04-01
期刊：
影响因子：
4.8
通讯作者：
Lietz, G.
中科院分区：
文献类型：
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作者：
Leung, W. C.;Hessel, S.;Lietz, G.
负责将β-胡萝卜素转化为视黄醛的关键酶是β-胡萝卜素15，15 '-单加氧酶（BCMO 1）。由于据报道，β-胡萝卜素转化为维生素A在高达45%的健康个体中是高度可变的，因此我们假设BCMO 1基因的遗传多态性可能有助于发生不良转化表型。在这里，我们描述了总的开放阅读框架的BCMO 1编码区，导致两个常见的非同义单核苷酸多态性（R267 S：rs 12934922; A379 V：rs7501331）的识别与变异等位基因频率分别为42和24%的筛选。体外生物化学分析表明，重组267 S +379 V双突变体的BCMO 1催化活性降低了57%（P
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