rs11057830 — SCARB1

SCARB1 — Your Gateway for HDL-Carried Vitamin E and Carotenoids

Every fat-soluble micronutrient you absorb --- vitamin E, beta-carotene, lutein, zeaxanthin --- faces a double barrier: the intestinal wall and then the liver. At both sites, a single receptor protein called SR-BI¹¹ SR-BI
Scavenger receptor class B type I, encoded by SCARB1 on chromosome 12q24; an integral membrane protein with a large hydrophobic tunnel that channels lipophilic molecules into cells (scavenger receptor class B type I, encoded by SCARB1) acts as the primary gateway. SR-BI is expressed in enterocytes lining the small intestine and in hepatocytes, where it performs the selective uptake of HDL²² HDL
High-density lipoprotein particles that carry fat-soluble vitamins and cholesterol from peripheral tissues back to the liver-associated lipids --- including cholesterol, tocopherols, and carotenoids. The rs11057830 variant lies within an intron of SCARB1. While it does not change the protein's amino acid sequence, it is a tag SNP for a haplotype that influences the receptor's functional expression or activity. People carrying more copies of the G allele show lower circulating alpha-tocopherol than those with the A allele, a relationship confirmed in multiple cohorts totaling over 7,000 individuals.

The Mechanism

SR-BI's lipid transport mechanism relies on a large hydrophobic tunnel that threads through the membrane. Lipid molecules associate with HDL particles docked at the receptor's extracellular domain, then pass through this tunnel into the cell. The selectivity of this tunnel³³ selectivity of this tunnel
Li et al. 2023 showed that blocking the cholesterol tunnel with a C384Y mutation abolishes the preferential uptake of lutein and zeaxanthin, while beta-carotene uptake is less affected explains why SCARB1 shows different uptake efficiencies for different carotenoids: the more hydrophilic xanthophylls (lutein, zeaxanthin) navigate the tunnel most efficiently, while the purely hydrophobic beta-carotene relies on it less. The key functional finding for vitamin E is dramatic: Reboul et al. 2006⁴⁴ Reboul et al. 2006
Reboul E et al. Scavenger receptor class B type I (SR-BI) is involved in vitamin E transport across the enterocyte. J Biol Chem, 2006 showed that blocking SR-BI with a specific inhibitor (BLT1) reduced alpha-tocopherol transport across cultured enterocytes by up to 80%. In mice overexpressing intestinal SR-BI, gamma-tocopherol bioavailability was 2.7-fold higher than in wild-type animals. This positions SR-BI as the dominant --- not merely contributing --- protein for vitamin E intestinal absorption. RS-BI also handles the final delivery step. In brain capillary endothelial cells, adenovirus-mediated SR-BI overexpression⁵⁵ adenovirus-mediated SR-BI overexpression
Goti D et al. Scavenger receptor class B, type I is expressed in porcine brain capillary endothelial cells and contributes to selective uptake of HDL-associated vitamin E. J Neurochem, 2001 produced a 4-fold increase in HDL-associated alpha-tocopherol uptake, demonstrating that SR-BI shapes vitamin E delivery not just at the gut but at every tissue that relies on HDL-mediated supply. How rs11057830 specifically alters SR-BI function is not fully characterized --- it may tag a haplotype affecting promoter activity, splicing, or a nearby regulatory element. What is established is the functional consequence: fewer copies of the A allele correlates with lower circulating tocopherol.

The Evidence

The primary evidence comes from a genome-wide association study⁶⁶ genome-wide association study
Major JM et al. Genome-wide association study identifies common variants associated with circulating vitamin E levels. Hum Mol Genet, 2011 conducted across 5,006 men of European descent in two cohorts, including the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. After controlling for age, BMI, cholesterol, and supplementation status, rs11057830 was associated with circulating alpha-tocopherol at genome-wide significance (P = 2.0 × 10⁻⁸). The A allele conferred higher levels (beta = +0.04 on a log scale per allele), with mean alpha-tocopherol increasing from 11.8 mg/L (GG) to 12.2 mg/L (GA) to 12.7 mg/L (AA). The finding was replicated in 992 men from the PLCO trial and 2,775 women from the Nurses' Health Study, with the combined meta-analysis reaching P = 8.2 × 10⁻⁹. Together with CYP4F2 rs2108622 and the APOA5 locus rs964184, rs11057830 explained 1.7% of the variance in circulating alpha-tocopherol. For carotenoids, related SCARB1 variants in strong linkage disequilibrium with rs11057830 (particularly rs11057841, r² ≈ 0.7) have been associated with serum lutein levels. A study of 302 healthy subjects⁷⁷ study of 302 healthy subjects
McKay GJ et al. Investigation of genetic variation in scavenger receptor class B, member 1 (SCARB1) and association with serum carotenoids. Ophthalmology, 2013 found that rs11057841 predicted a 24% increase in serum lutein per T allele (P < 0.01 after permutation correction), with independent replication in the TwinsUK and CAREDS cohorts. Given the strong LD between rs11057841 and rs11057830, this carotenoid association likely applies to the same functional haplotype.

Practical Implications

The 7--8% difference in circulating alpha-tocopherol between GG and AA genotypes is modest in absolute terms. However, for GG carriers --- roughly 73% of people --- it represents the lower end of normal SR-BI-mediated uptake. Because SR-BI accounts for up to 80% of intestinal vitamin E transport, optimizing dietary delivery is directly relevant. Two factors amplify practical impact. First, vitamin E absorption is highly fat-dependent --- consuming it with a meal containing dietary fat improves micellarization and SR-BI access. Second, the natural RRR-alpha-tocopherol form is more efficiently retained by the liver (through the alpha-tocopherol transfer protein, alpha-TTP) than synthetic dl-alpha-tocopherol; for people with already-reduced SR-BI uptake, maximizing what reaches the liver is important. The carotenoid connection is worth noting. Beta-carotene, lutein, and zeaxanthin all use SR-BI for intestinal absorption. GG carriers absorbing less through this pathway may benefit from optimizing carotenoid bioavailability --- eating cooked rather than raw vegetables, pairing with fat, and favoring foods with high carotenoid density.

Interactions

This variant acts at the absorption step of the vitamin E pathway. A functionally distinct step is handled by rs6994076 in TTPA, which governs how much alpha-tocopherol the liver redistributes to tissues via VLDL particles. Individuals who carry both rs11057830 GG (reduced SR-BI absorption) and rs6994076 TT (reduced alpha-TTP expression) face compounded limitations: less vitamin E absorbed through the intestine AND less efficiently retained and distributed by the liver. This combination represents the most actionable double-hit in the vitamin E pathway, warranting both dietary and supplementation attention. The compound effect of GG at rs11057830 + TT at rs6994076 should be modeled as a compound action recommending higher-dose natural tocopherol supplementation with fat-rich meals. For carotenoids, rs12934922 in BCO1 (beta-carotene 15,15'-oxygenase) interacts with SCARB1 at a downstream step: rs11057830 determines how much beta-carotene enters the body; BCO1 rs12934922 determines how efficiently it is converted to retinol. Poor converters (BCO1 TT) who also carry SCARB1 GG absorb less beta-carotene AND convert less of it to vitamin A.