Is CD36 rs1761667 AA associated with altered CD36 expression and fatty-acid uptake or trafficking?

The CD36 gene encodes a vital scavenger receptor and transporter that mediates long-chain fatty acid uptake and intracellular trafficking. The rs1761667 single nucleotide polymorphism, located in the regulatory 5′ flanking promoter region of the gene, plays a critical role in modulating these processes, particularly in individuals with the homozygous AA genotype.

Molecular expression and regulation

• Reduced Gene Expression: The minor A allele acts as a low-expression cis-expression quantitative trait locus (cis-eQTL). Individuals with the homozygous AA genotype exhibit a dose-dependent reduction in CD36 mRNA and protein expression across various cell types, including circulating monocytes, platelets, and taste papillae.

Physiological and sensory mechanisms

• Impaired Oral Fat Sensing: Decreased CD36 expression on the surface of taste cells directly elevates the oral detection threshold for long-chain fatty acids, such as oleic acid.
• Compensatory Dietary Habits: This reduction in oral fat taste sensitivity is linked to behavioral adaptations, specifically an increased preference for and higher habitual consumption of dietary fats.
• Lipid Trafficking and Metabolism: The AA genotype is associated with distinct baseline metabolic profiles, including alterations in serum triglycerides and HDL cholesterol. While cellular fatty acid absorption and intracellular trafficking are biologically compromised by reduced CD36 availability, direct human pharmacokinetic or tracer-based evidence confirming altered systemic lipid absorption remains limited.

Bottom line

• The CD36 rs1761667 AA genotype is a established genetic modifier that reduces CD36 expression, impairs oral lipid detection, and is highly plausible to alter systemic fatty acid trafficking and baseline lipid profiles.