The association of fatty acid-binding protein 2 A54T polymorphism with postprandial lipemia depends on promoter variability.

Studies on the association of fatty acid-binding protein 2 (FABP2) A54T and promoter polymorphism, and type 2 diabetes mellitus, insulin, and triglyceride levels are controversial. The aim of this study was to investigate the interfering effect of FABP2 A54T and promoter polymorphism on the postprandial response to a mixed meal and an oral glucose load. Seven hundred men from the Metabolic Intervention Cohort Kiel underwent a standard glucose tolerance test and a standardized mixed meal test and were genotyped by use of the Taqman method. When calculated independently from promoter variability, postprandial triglyceride levels were significantly higher and postprandial insulin sensitivity (homeostasis model assessment index) was lower in homozygous carriers of FABP2 T54T compared with carriers of the FABP2 exon wild-type allele (FABP2 A54A and A54T). This confirms previous findings. The effect of the exon T54T genotype on triglyceride levels and insulin sensitivity, however, was dependent on promoter variability. We found a significant increase in postprandial triglyceride levels and a decrease in insulin sensitivity due to T54T only in the presence of the homozygous B genotype at the promoter polymorphism. Similar results were obtained after oral glucose tolerance test. Reporter gene assays indicated a higher responsiveness to peroxisome proliferator-activating receptor-gamma (PPAR-gamma)/retinoid X receptor (RXR) of FABP2 promoter B vs promoter A. Synergism between a higher inducibility of FABP2 expression and a higher activity of T54 variant may explain higher postprandial triglycerides in case of combined genotype (promoter B + T54). This interference and different linkage disequilibrium between FABP2 exon and promoter polymorphisms may explain the different results obtained in different cohorts.