rs7501331 — BCO1 Ala379Val

BCO1 Ala379Val -- Are You a Beta-Carotene Poor Converter?

The BCO1 gene (formerly called BCMO1) encodes beta-carotene 15,15'-monooxygenase¹¹ beta-carotene 15,15'-monooxygenase
The enzyme that cleaves one molecule of beta-carotene into two molecules of retinal, which is then converted to retinol (vitamin A), the key enzyme responsible for converting beta-carotene from plant foods into retinol -- the form of vitamin A your body actually uses. This single enzymatic step is the only route by which dietary carotenoids from carrots, sweet potatoes, spinach, and other orange and green vegetables become biologically active vitamin A.

The rs7501331 variant causes an alanine-to-valine substitution at position 379 of the BCO1 protein. Carriers of the T allele produce a less efficient enzyme, meaning more beta-carotene passes through unconverted. This is one of two coding variants in BCO1 (alongside rs12934922²² rs12934922
R267S, the other common BCMO1 coding variant with a 42% minor allele frequency) that together explain much of the genetically determined variation in beta-carotene conversion efficiency across the population.

The Mechanism

BCO1 is a non-heme iron oxygenase³³ non-heme iron oxygenase
It requires iron as a cofactor and molecular oxygen to cleave the central 15,15' double bond of beta-carotene expressed primarily in intestinal enterocytes and the liver. It cleaves beta-carotene symmetrically at the central 15,15' double bond, producing two molecules of retinal⁴⁴ retinal
Also called retinaldehyde; this is subsequently reduced to retinol (vitamin A) by retinal reductase. The Ala379Val substitution occurs within the catalytic domain, subtly altering the enzyme's active site geometry and reducing its turnover rate.

The body has a feedback mechanism: when retinol levels are adequate, an intestinal transcription factor⁵⁵ intestinal transcription factor
ISX (intestine-specific homeobox) represses BCO1 transcription when retinoic acid levels are sufficient downregulates BCO1 expression to prevent vitamin A toxicity. In people with reduced BCO1 activity, this feedback loop still operates, but the baseline conversion capacity is lower, meaning less vitamin A is produced from a given amount of dietary beta-carotene even before feedback suppression kicks in.

The Evidence

The landmark 2009 study by Leung et al.⁶⁶ 2009 study by Leung et al.
Leung WC et al. Two common single nucleotide polymorphisms in the gene encoding beta-carotene 15,15'-monoxygenase alter beta-carotene metabolism in female volunteers. FASEB J, 2009 identified rs7501331 (A379V) and rs12934922 (R267S) as the two common coding variants responsible for the "poor converter" phenotype. Female volunteers carrying the 379V allele showed a 32% reduction in the retinyl palmitate-to-beta-carotene ratio after a pharmacological beta-carotene dose (P = 0.005). Those carrying both variant alleles (379V + 267S) showed a 69% reduction (P = 0.001). In vitro, the double mutant enzyme had 57% lower catalytic activity (P < 0.001).

Carriers also had dramatically higher fasting plasma beta-carotene: +160% for 379V carriers and +240% for double carriers. This accumulation of unconverted beta-carotene is the biochemical signature of poor converter status and can manifest as carotenodermia⁷⁷ carotenodermia
A harmless yellowing of the skin, especially the palms and soles, caused by excess circulating carotenoids in extreme cases.

A large study in 2,344 women⁸⁸ large study in 2,344 women
Hendrickson SJ et al. BCO1 SNPs in relation to plasma carotenoid and retinol concentrations in women of European descent. Am J Clin Nutr, 2012 of European descent confirmed that BCO1 genetic variants predict plasma carotenoid levels and can serve as surrogate markers for carotenoid exposure in epidemiological studies.

In Filipino children and adolescents, Zumaraga et al. (2022)⁹⁹ Zumaraga et al. (2022)
Zumaraga MPP et al. Genotype effects on beta-carotene conversion to vitamin A. Food Nutr Bull, 2022 found the A379V T allele was inversely associated with vitamin A status in a cohort of 693 subjects, highlighting the relevance of this variant for populations that depend heavily on plant-based provitamin A sources.

Borel et al. (2011)¹⁰¹⁰ Borel et al. (2011)
Borel P et al. Genetic variants in BCMO1 and CD36 are associated with plasma lutein concentrations and macular pigment optical density. Ann Med, 2011 found that rs7501331 genotype also affects macular pigment optical density and plasma lutein levels, suggesting BCO1 variants influence the metabolism of multiple carotenoids beyond beta-carotene alone.

Practical Implications

The clinical relevance of rs7501331 depends heavily on dietary context. For people eating a mixed diet with adequate preformed vitamin A from eggs, dairy, fish, and liver, reduced beta-carotene conversion is largely inconsequential -- the body gets retinol directly from animal sources regardless of BCO1 efficiency.

The variant becomes clinically meaningful for vegans, vegetarians, and anyone relying primarily on plant sources for vitamin A. A person with two T alleles who eats no animal products may struggle to maintain adequate retinol status from beta-carotene alone, particularly if their diet is also low in fat (since beta-carotene absorption requires dietary fat).

Signs of suboptimal vitamin A status include dry eyes, night vision difficulty, dry skin, and impaired immune function. A serum retinol test can clarify actual status regardless of genotype.

Interactions

The most important interaction is with rs12934922 (R267S), the other common BCO1 coding variant. Individuals carrying T alleles at both rs7501331 and rs12934922 have compound poor converter status with up to 69% reduced beta-carotene conversion -- far exceeding the effect of either variant alone. The R267S variant has a higher minor allele frequency (42%) than A379V (24%), making the double-carrier combination relatively common. In the Leung et al. study, about 7-8% of the population carried both variant alleles.

This compound interaction is well-documented and represents one of the clearest gene-gene interactions in nutritional genomics. For double carriers who are vegan or vegetarian, preformed vitamin A supplementation (retinyl palmitate or retinol) or regular consumption of retinol-rich foods becomes particularly important.