The human intestinal fatty acid binding protein 2 (FABP2) mediates fat 
absorption by binding and intracellular trafficking of long-chain free fatty 
acids. Studies with knockout mice and association analysis of polymorphisms 
revealed that FABP2 is a susceptibility gene for type 2 diabetes (noninsulin 
dependent diabetes mellitus [NIDDM]) and related traits. Relevant FABP2 promoter 
polymorphisms c.-80_-79insT (rs5861422), c.-136_-132delAGTAG (rs5861423), 
c.-168_-166delAAGinsT (rs1973598), c.-260G>A (rs6857641), c.-471G>A (rs2282688), 
and c.-778G>T (rs10034579) result in two haplotypes A and B, whereby B possesses 
two- to three-fold lower transcriptional activity than A. We show in luciferase 
reporter gene assays by a series of chimeric FABP2 promoter constructs in 
intestinal Caco-2 cells that polymorphism c.-80_-79insT essentially determines 
different activities of the FABP2 promoter. In accordance, in electrophoretic 
mobility shift assays (EMSAs), transcriptional factors GATA-5 and -6 bind with 
higher binding affinities to the FABP2 promoter region containing the -80A 
allele compared to B. As functional consequence, haplotype A is twice as much 
more activated by GATA factors than haplotype B in liver Huh7 cells. 
Additionally, a construct bearing the -80B allele in the background of haplotype 
A reversed the activity from A to B. Thus, the GATA mediated differential 
activation of FABP2 haplotypes depends on polymorphism c.-80_-79insT. This 
provides the molecular basis for the variant specific transcriptional regulation 
of the diabetes type 2-associated FABP2 gene.