rs1799883 — FABP2 Ala54Thr

FABP2 — Fat Absorption Efficiency

FABP2 (Fatty Acid Binding Protein 2) is expressed in intestinal cells and is responsible for intracellular transport of dietary fatty acids¹¹ Inside enterocytes (intestinal absorptive cells), FABP2 shuttles fatty acids from the cell membrane to the endoplasmic reticulum for processing.

The Mechanism

The Ala54Thr variant (rs1799883) is a missense mutation in exon 2 of FABP2, where an adenine replaces guanine at the DNA level, substituting alanine with threonine at position 54 of the protein (p.Ala54Thr). Baier et al.²² Baier et al.
Baier et al. An amino acid substitution in the human intestinal fatty acid binding protein is associated with increased fatty acid binding, increased fat oxidation, and insulin resistance. J Biol Chem, 1995 demonstrated that the threonine-containing protein has a 2-fold greater affinity for long-chain fatty acids than the alanine-containing protein, leading to more efficient fat absorption from the intestine.

The Evidence

The original discovery by Baier et al.³³ original discovery by Baier et al.
Baier et al. J Biol Chem, 1995 in Pima Indians showed that Thr54 carriers had higher fasting insulin, lower insulin-stimulated glucose uptake, and higher fat oxidation rates. The threonine variant increases the protein's affinity for long-chain fatty acids by approximately 2-fold.

Carriers of the Thr allele absorb more calories from fat⁴⁴ Studies estimate Thr carriers may absorb roughly 20-30% more long-chain fatty acids per meal than Ala/Ala individuals, which can contribute to weight gain when fat intake is high.

A meta-analysis by Zhao et al.⁵⁵ meta-analysis by Zhao et al.
Zhao et al. Association between FABP2 Ala54Thr polymorphisms and T2DM risk: a HuGE review and meta-analysis. Lipids Health Dis, 2014 found significant associations with type 2 diabetes in Asian populations (OR 1.19, 95% CI 1.05-1.36) but not in Caucasians. The evidence for obesity association is mixed, with some meta-analyses finding no significant effect on BMI.

Practical Implications

The Thr allele is common across all populations (24-33% frequency), with slightly higher frequency in South Asian and East Asian groups. The practical significance is moderate — this variant matters most when combined with high dietary fat intake, where increased absorption efficiency can contribute to excess calorie intake and insulin resistance.

Interactions

FABP2 Ala54Thr interacts with total dietary fat intake — the variant's metabolic effects are more pronounced on high-fat diets. If you also carry TCF7L2 risk alleles (rs7903146), moderating fat intake becomes doubly important.