A Combination of Single-Nucleotide Polymorphisms Is Associated with Interindividual Variability in Dietary β-Carotene Bioavailability in Healthy Men

Borel, Patrick; Desmarchelier, Charles; Nowicki, Marion; Bott, Raoul

doi:10.3945/jn.115.212837

Cited by 71 publications

(72 citation statements)

References 59 publications

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“…This precludes the use of GWAS, due to lack of power, and requires the use of candidate gene association studies to identify genetic variants involved. These studies were dedicated to βC metabolism and measured either postprandial chylomicron βC [113] or postprandial triglyceride-rich lipoprotein βC and RP concentrations [114,115] after test meals that provided βC. Thus, there is still no data on genetic variations associated with postprandial blood RP concentrations after a test meal rich in preformed VA. Consequently, it is obvious that the observations/conclusions presented in this chapter will be significantly improved in the future.…”

Section: Genetic Variations That Have Been Suggested To Modulate Bmentioning

confidence: 99%

“…Thus, there is still no data on genetic variations associated with postprandial blood RP concentrations after a test meal rich in preformed VA. Consequently, it is obvious that the observations/conclusions presented in this chapter will be significantly improved in the future. In the study dedicated to identifying genetic variations associated with βC bioavailability [113], it was observed that the variability in the postprandial blood βC response (Area under the curve of the 0–8 h postprandial chylomicron βC concentrations) was associated with a combination of 25 SNPs in or near 12 candidate genes. Four of these genes were involved in the postprandial chylomicron triacylglycerol response in the same group of subjects [91], which was not surprising, as newly-absorbed βC is carried from the intestine to the liver via chylomicrons.…”

Section: Genetic Variations That Have Been Suggested To Modulate Bmentioning

confidence: 99%

“…Nevertheless, eight of these genes were specifically associated with the βC response. Possible explanations why these genes were associated with the βC response are discussed in the original paper [113]. Nevertheless, two associations deserve closer attention.…”

Section: Genetic Variations That Have Been Suggested To Modulate Bmentioning

confidence: 99%

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Genetic Variations Associated with Vitamin A Status and Vitamin A Bioavailability

2017

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Blood concentration of vitamin A (VA), which is present as different molecules, i.e., mainly retinol and provitamin A carotenoids, plus retinyl esters in the postprandial period after a VA-containing meal, is affected by numerous factors: dietary VA intake, VA absorption efficiency, efficiency of provitamin A carotenoid conversion to VA, VA tissue uptake, etc. Most of these factors are in turn modulated by genetic variations in genes encoding proteins involved in VA metabolism. Genome-wide association studies (GWAS) and candidate gene association studies have identified single nucleotide polymorphisms (SNPs) associated with blood concentrations of retinol and β-carotene, as well as with β-carotene bioavailability. These genetic variations likely explain, at least in part, interindividual variability in VA status and in VA bioavailability. However, much work remains to be done to identify all of the SNPs involved in VA status and bioavailability and to assess the possible involvement of other kinds of genetic variations, e.g., copy number variants and insertions/deletions, in these phenotypes. Yet, the potential usefulness of this area of research is exciting regarding the proposition of more personalized dietary recommendations in VA, particularly in populations at risk of VA deficiency.

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Section: Genetic Variations That Have Been Suggested To Modulate Bmentioning

confidence: 99%

Section: Genetic Variations That Have Been Suggested To Modulate Bmentioning

confidence: 99%

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Genetic Variations Associated with Vitamin A Status and Vitamin A Bioavailability

2017

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“…Although SNPs were not measured in this study, previous work demonstrated that differences between circulating concentrations of a-and b-carotene were correlated to the same SNP in intron 5 of SR-B1 (34). Similarly, SNPs affiliated with the gene encoding for intestine specific homeobox, a transcriptional repressor of the SR-B1 transporter, as well as 4 genes involved in chylomicron response, were significantly correlated with postprandial b-carotene absorption (35). No study to our knowledge has yet assessed the effects of these SNPs on the differential uptake of a-carotene compared with b-carotene.…”

Section: Discussionmentioning

confidence: 94%

“…The reduced binding affinity could be attributable to the shift of a single double bond out of conjugation to form an e-ring, allowing free rotation around the 6-7 bond in a-carotene (6). Studies revealed that SNPs in human BCO1 result in variable conversion of provitamin A carotenoids (35,(38)(39)(40). It is plausible that some of these SNPs result in enzymes with altered conformation, which could also affect provitamin A binding affinity.…”

Section: Discussionmentioning

confidence: 99%

Relative contribution of α-carotene to postprandial vitamin A concentrations in healthy humans after carrot consumption

Cooperstone¹,

H²,

Riedl³

et al. 2017

The American Journal of Clinical Nutrition

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Background: Asymmetric a-carotene, a provitamin A carotenoid, is cleaved to produce retinol (vitamin A) and a-retinol (with negligible vitamin A activity). The vitamin A activity of a-carotenecontaining foods is likely overestimated because traditional analytic methods do not separate a-retinol derivatives from active retinol.Objective: This study aimed to accurately characterize intestinal a-carotene cleavage and its relative contribution to postprandial vitamin A in humans after consumption of raw carrots. Design: Healthy adults (n = 12) consumed a meal containing 300 g raw carrot (providing 27.3 mg b-carotene and 18.7 mg a-carotene). Triglyceride-rich lipoprotein fractions of plasma were isolated and extracted, and a-retinyl palmitate (aRP) and retinyl palmitate were measured over 12 h postprandially via highperformance liquid chromatography-tandem mass spectrometry. The complete profile of all a-retinyl esters and retinyl esters was measured at 6 h, and total absorption of a-and b-carotene was calculated. Results: aRP was identified and quantified in every subject. No difference in preference for absorption of b-over a-carotene was observed (adjusting for dose, 28% higher, P = 0.103). After absorption, b-carotene trended toward preferential cleavage compared with a-carotene (22% higher, P = 0.084). A large range of provitamin A carotenoid conversion efficiencies was observed, with a-carotene contributing 12-35% of newly converted vitamin A (predicted contribution = 25.5%). In all subjects, a majority of a-retinol was esterified to palmitic acid (as compared with other fatty acids). Conclusions: a-Retinol is esterified in the enterocyte and transported in the blood analogous to retinol. The percentage of absorption of a-carotene from raw carrots was not significantly different from b-carotene when adjusting for dose, although a trend toward higher cleavage of b-carotene was observed. The results demonstrate large interindividual variability in a-carotene conversion. The contribution of newly absorbed a-carotene to postprandial vitamin A should not be estimated but should be measured directly to accurately assess the vitamin A capacity of a-carotenecontaining foods. This trial was registered at clinicaltrials.gov as NCT01432210.Am J Clin Nutr 2017;106:59-66.

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New associations of serum β‐carotene, lycopene, and zeaxanthin concentrations with NR1H3, APOB, RDH12, AND CYP genes

Domarkienė

Mažeikienė

Petrauskaitė

et al. 2022

Food Science & Nutrition

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Variation in carotenoid bioavailability at individual and population levels might depend on host‐related factors where genetic variation has a part to play. It manifests itself through the proteins involved in carotenoid intestinal absorption and metabolism, blood lipoprotein transport, or tissue uptake. This study aims to identify novel SNPs which could be associated with carotenoid serum concentrations. A total of 265 self‐reported healthy individuals of Lithuanian origin were genotyped (Illumina HumanOmniExpress‐12v1.0 or v1.1 and Infinium OmniExpress‐24v1.2 arrays) and fasting blood serum concentrations of β‐ and α‐carotene, β‐cryptoxanthin, lycopene, lutein, and zeaxanthin were measured (Shimadzu Prominence HPLC system). According to the individual carotenoid concentrations, the cohort was subdivided into quartiles. Q1 and Q4 were used for the following association analysis. The set of 2883 SNPs in 109 potential candidate genes (assumed for a direct or indirect role in carotenoid bioavailability) was analyzed. Liver X receptor alpha (NR1H3) “transport” polymorphisms rs2279238 (p = 2.129 × 10−5) and rs11039155 (p = 2.984 × 10−5), and apolipoprotein B (APOB) “transport” polymorphism rs550619 (p = 4.844 × 10−5) were associated with higher zeaxanthin concentration. Retinol dehydrogenase 12 (RDH12) “functional partner” polymorphism rs756473 (p = 7.422 × 10−5) was associated with higher lycopene concentration. Twenty‐one cytochrome P450 (CYP2C9, CYP2C18, and CYP2C19) “metabolism” polymorphisms in locus 10q23.33 were significantly associated with higher β‐carotene concentration. To conclude, four novel genomic loci were found to be associated with carotenoid serum levels. Zeaxanthin, lycopene, and β‐carotene serum concentrations might depend on genetic variation in NR1H3, APOB, RDH12 and CYP2C9, CYP2C18, and CYP2C19 genes.

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A Combination of Single-Nucleotide Polymorphisms Is Associated with Interindividual Variability in Dietary β-Carotene Bioavailability in Healthy Men

Cited by 71 publications

References 59 publications

Genetic Variations Associated with Vitamin A Status and Vitamin A Bioavailability

Genetic Variations Associated with Vitamin A Status and Vitamin A Bioavailability

Relative contribution of α-carotene to postprandial vitamin A concentrations in healthy humans after carrot consumption

New associations of serum β‐carotene, lycopene, and zeaxanthin concentrations with NR1H3, APOB, RDH12, AND CYP genes

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