Does the FABP2 rs1799883 AA genotype increase post-meal triglycerides?

At age 53, the clinical relevance of FABP2 variation is mainly as a possible modifier of post-meal lipid handling, not a stand-alone determinant of lipid risk. Here, “AA” must be confirmed as DNA-level Thr54/Thr54; nomenclature can otherwise be reversed.

Clinical evidence

• The claim is plausible with moderate confidence, but is not established as a uniform effect. In a 15-person oral fat-loading study, Thr54 homozygotes had higher triglyceride exposure than Ala54 homozygotes (AUC 4.27 ± 1.31 vs 2.49 ± 1.18 mmol/L·h; P=0.04).
• A larger abbreviated fat-tolerance study similarly found higher 4-hour triglycerides and triglyceride AUC in Thr54 carriers, although substantial post-meal triglyceride elevations also occurred independently of genotype.
• Findings are inconsistent across settings. Healthy nonobese participants given three fat types showed no main genotype effect on chylomicron-triglyceride AUC, and in type 2 diabetes, triglyceride responses did not differ by genotype despite differences in chylomicron fatty-acid composition.

Absorption and mechanisms

• Small meal studies found greater postprandial chylomicron unsaturated-fatty-acid responses in Thr54/Thr54 individuals; one diabetes cohort included 11 Thr54/Thr54 and 15 Ala54/Ala54 participants. Earlier work also reported higher postprandial C14–C18 fatty acids in chylomicron/VLDL triglycerides.
• These are compatible with enhanced intestinal lipid processing and transport, but do not prove greater total fatty-acid absorption. Direct marker-based evidence found only small effects on individual fatty acids, sometimes slightly lower absorption.
• Mechanistically, Thr54 FABP2 has approximately twofold greater in-vitro affinity for long-chain fatty acids and may enhance enterocyte fatty-acid transport and triglyceride/chylomicron secretion.

Bottom line

• AA/Thr54 homozygosity may predispose to greater post-meal chylomicron fatty-acid transport and, under some dietary or metabolic conditions, higher triglycerides; it does not establish broadly increased intestinal fat absorption or a reliably larger triglyceride response in every person.