Genetic Variations Associated with Vitamin A Status and Vitamin A Bioavailability

Abstract

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.

A Functional Binding Domain in the Rbpr2 Receptor is Required for Vitamin A Transport, Ocular Retinoid Homeostasis, and Photoreceptor Cell Survival in Zebrafish

“…Dietary or maternal derived vitamin A (all-trans retinol) and its metabolites (retinoids) regulate many biological and cellular processes, including metabolism, differentiation and proliferation, and is essential for embryonic development, immune function, reproduction, and vision in humans [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. Vitamin A deficiency or excess during development affects many vertebrate organs, including the eye [4,5,[15][16][17][18][19][20][21]. The most well-known early effects of vitamin A deficiency in humans is night blindness [22,23], while prolonged vitamin A deficiency during pregnancy has been attributed to increased microphthalmia, childhood mortality and morbidity, and photoreceptor cell death and progressive vision loss in adulthood [24][25][26][27].…”

“…Dietary vitamin A is the precursor for at least two critical metabolites, all-trans retinoic acid (atRA) and 11-cis retinaldehyde (11-cis RAL) [16]. Evolution's choice of dietary vitamin A as a precursor for the vital signaling molecule (at-RA) for retinal cell development and maintenance, and the essential visual chromophore (11-cis RAL) in photoreceptors, triggered selective pressure to advance an efficient system of transporters for dietary vitamin A uptake and storage [5,10,11,28,29]. All-trans retinol (ROL) is the main transport form of dietary vitamin A in the blood.…”

“…STRA6 binds to RBP4 with high affinity and specificity, and this facilitates cellular uptake and intracellular transport of ROL from holo-RBP4 into the retinal pigmented epithelium (RPE). However, STRA6 is not expressed in the liver, intestine, lungs, and other peripheral tissues proposed to express a membrane receptor that's mediates systemic uptake and peripheral tissue storage of food-derived ROL [2,5,49,32]. Likewise, while we and others have shown that the scavenger receptor class B type 1 (SR-B1) protein is involved in cellular uptake of dietary pro-vitamin A carotenoids for ROL production, SR-B1 is not involved in RBP4-ROL transport [34][35][36][37].…”

“…Previously, the existence of a second RBP4 receptor expressed in tissues lacking STRA6 was postulated [2,5], and in 2013, the retinol binding protein 4 receptor 2 or stimulated by retinoic acid 6 like protein (RBPR2/STRA6L) was molecularly identified [2].…”

Transcription factor ISX mediates the cross talk between diet and immunity

“…Common single-nucleotide polymorphisms in ISX, BCO1, or SCARB1 genes affect serum BC levels in humans, suggesting that the role of ISX in the control of intestinal BCO1 activity is well conserved (11). However, several studies indicate that the ISX protein may serve additional functions (6).…”