rs3211867 — CD36

Intronic CD36 variant that reduces CD36 expression, with effects on circulating sCD36.

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CD36 and the Fat Sensor You Never Knew You Had

Before a single drop of dietary fat reaches your bloodstream, your body is already preparing for it. CD36 — the fatty acid translocase — sits on the surface of taste bud cells, intestinal enterocytes, and dozens of other cell types, acting as the primary sensor and gatekeeper for long-chain dietary fats. rs3211867 is an intronic variant in the CD36 gene that reduces how much of this protein is produced, with measurable downstream effects on circulating CD36 levels.

The Mechanism

CD36 operates simultaneously in at least three contexts relevant to lipid metabolism. In circumvallate taste buds11 In circumvallate taste buds
CD36 initiates fat taste perception and the cephalic phase of digestion, triggering anticipatory digestive signals before fat even enters the gut. In intestinal enterocytes, CD36 binds long-chain fatty acids and facilitates their packaging into chylomicrons — the lipid particles that transport dietary fat through the lymph into the bloodstream. In macrophages, CD36 mediates uptake of oxidized LDL and modulates pro-inflammatory signaling22 pro-inflammatory signaling
CD36 in macrophages drives foam cell formation; reduced expression is locally protective.

rs3211867 is a C→A substitution in intron 3 of the CD36 gene. Like several other CD36 intronic variants, it functions as an [expression quantitative trait locus (eQTL) | eQTL: a genetic variant that influences how much mRNA/protein a gene produces, without changing the protein sequence itself], influencing CD36 transcription. Circulating soluble CD36 (sCD36) — shed from cell surfaces and measurable in plasma — drops significantly in A allele carriers compared to CC homozygotes in healthy controls (p = 0.02)33 in healthy controls (p = 0.02)
Toure et al. BMC Medical Genomics 2022, PMID 36031603.

The Evidence

Toure et al. (2022)44 Toure et al. (2022) examined 100 Senegalese women (50 controls, 50 with type 2 diabetes). In healthy controls, CC genotype carriers had significantly higher sCD36 levels than AA/AC carriers (3,889 vs 1,745 pg/mL; p = 0.02).

The picture is complex: reducing CD36 in macrophages is atherogenic-protective (less oxidized-LDL uptake, less foam cell formation), but reducing CD36 in enterocytes worsens [postprandial hypertriglyceridemia | elevated blood triglycerides in the hours after eating, associated with cardiovascular risk].

An early study by Bokor et al. (2010)55 Bokor et al. (2010) reported OR = 1.96 for early-onset obesity in European adolescents carrying the A allele. However, a subsequent meta-analysis in 9,973 European subjects found no significant obesity association (Choquet et al. 2011, PMID 2096690466 Choquet et al. 2011, PMID 20966904), limiting confidence in the obesity link specifically.

Nutrient Interactions

dietary fat (long-chain fatty acids) altered_metabolism
omega-3 fatty acids (EPA/DHA) altered_metabolism

Genotype Interpretations

What each possible genotype means for this variant.

CC Normal CD36 Expression Normal

Normal CD36 expression and fat sensing

You carry two copies of the common C allele at rs3211867. This is the reference genotype — your CD36 gene is not influenced by this particular intronic variant, and your circulating soluble CD36 levels are expected to be in the normal range. About 77% of people globally share this genotype, though it is more prevalent in Europeans (~85%) than in African or East Asian populations (~50%).

AC Reduced CD36 Expression Reduced

One A allele — moderately reduced CD36 expression

You carry one A allele at this intronic CD36 position, which is associated with reduced CD36 gene expression and lower circulating soluble CD36 (sCD36) levels. Roughly 21% of people carry this AC genotype. The reduction in CD36 is partial.

AA Low CD36 Expression Reduced

Two A alleles — low CD36 expression, impaired postprandial fat handling

You carry two copies of the A allele at rs3211867, the rarest genotype (~1.5% globally). In healthy controls, AA/AC carriers had sCD36 levels averaging 1,745 pg/mL versus 3,889 pg/mL in CC carriers — a greater than 50% reduction.