title: Single nucleotide polymorphisms upstream from the β-carotene 15,15'-monoxygenase gene influence provitamin A conversion efficiency in female volunteers.
abstract: β-Carotene, the most abundant provitamin A carotenoid in the diet, is converted to retinal by β-carotene 15,15'-monoxygenase (BCMO1). However, β-carotene absorption and conversion into retinal is extremely variable among individuals, with proportions of low responders to dietary β-carotene as high as 45%. Recently, 2 common nonsynonymous single nucleotide polymorphisms (SNPs) within the BCMO1 coding region (R267S; rs12934922 and A379V; rs7501331) revealed reduced catalytic activity, confirming that genetic variations contribute to the low responder phenotype. Because 4 SNPs 5' upstream from the BCMO1 gene were recently shown to affect circulating carotenoid concentrations, the current study aimed to investigate the effects of these SNPs on β-carotene conversion efficiency. Three of the 4 polymorphisms (rs6420424, rs11645428, and rs6564851) reduced the catalytic activity of BCMO1 in female volunteers by 59, 51, and 48%, respectively. The TG-rich lipoprotein fraction retinyl palmitate:β-carotene ratio was negatively correlated with the G allele of rs11645428 (r = -0.44; P = 0.018), whereas it was positively correlated with the G allele of rs6420424 (r = 0.53; P = 0.004) and the T allele of rs6564851 (r = 0.41; P = 0.028). Furthermore, large inter-ethnic variations in frequency of affected alleles were detected, with frequencies varying from 43 to 84% (rs6420424), 52 to 100% (rs11645428), and 19 to 67% (rs6564851). In summary, a range of SNPs can influence the effectiveness of using plant-based provitamin A carotenoids to increase vitamin A status in at-risk population groups and this effect may vary depending on ethnic origin.
authors: Human Nutrition Research Centre, Newcastle University, Newcastle upon Tyne, UK. georg.lietz@ncl.ac.uk
authors: Georg
authors: G
authors: Lietz
authors: Anthony
authors: A
authors: Oxley
authors: Wing
authors: W
authors: Leung
authors: John
authors: J
authors: Hesketh
mesh_terms: D000328:Adult; D005260:Female; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D014801:Vitamin A / Q000378:metabolism*; D050559:beta-Carotene 15,15'-Monooxygenase / Q000235:genetics* / Q000378:metabolism
chemical_list: D014801:Vitamin A; D050559:beta-Carotene 15,15'-Monooxygenase