Postprandial Hypertriglyceridemia Is Associated with the Variant 54 Threonine FABP2 Gene.

Purpose: Fasting or postprandial hypertriglyceridemia is considered an independent cardiovascular disease (CVD) risk factor. The intestinal fatty acid binding protein (FABP2) is involved in the intracellular transport and metabolism of fatty acids. The presence of the Ala54Thr polymorphism of the FABP2 gene appears to be involved in postprandial hypertriglyceridemia. We explored the possible association of the Ala54Thr polymorphism with fat intolerance in apparently healthy, fasting, normolipidemic subjects with normal body-mass index and without diabetes. Methodology: A total of 158 apparently healthy individuals were classified as fat tolerant (n = 123) or intolerant (n = 35) according to their response (plasma triglycerides) to an oral abbreviated tolerance test with blood samples taken at 0, 2 and 4 h. At 0 h, all subjects ingested 26.3 g of fats. Presence of the Ala54Thr polymorphism of the FABP2 gene was evaluated by polymerase chain reaction⁻restriction fragment length (PCR⁻RFLP). Results: The group with fat intolerance (postprandial hypertriglyceridemia group) showed an increased frequency of the Thr54Thr genotype when compared with the group with normal fat tolerance (control group) (23% vs. 4%, respectively, OR: 16.53, 95% CI: 4.09⁻66.82, p: 0.0001, pc: 0.0003). Carriers of at least one Thr54 allele were up to six times more prevalent in the fat intolerant group than in the non-carriers. (OR: 6.35; 95% CI: 1.86⁻21.59, p: 0.0003, pc: 0.0009). The levels of plasma triglycerides (Tg) at 4 h after the test meal were higher in carriers of at least one 54Thr allele than in carriers of the Ala54 allele (p < 0.05). Conclusions: There is a significant association between postprandial hypertriglyceridemia and the presence of at least one 54Thr allele of the FABP2 gene. In addition, subjects with this genotype showed an increased ratio of Tg/HDL-cholesterol. This parameter is a marker of increased CVD risk and insulin resistance.

Fat Intolerance in Apparently Healthy Individuals with Normal Fasting Lipoproteins Is Associated with Markers of Cardiovascular Risk.

BACKGROUND: Postprandial increase of triglyceride-rich lipoproteins augments the risk of atherosclerotic cardiovascular disease and all-cause mortality. We explored the hypothesis that a simplified oral fat tolerance test can uncover differences in postprandial triglyceride response associated with potentially atherogenic lipoprotein characteristics, even in a cohort of apparently healthy 31-year-old [mean (SD), 31 (11)] nonobese individuals with normal fasting lipids and lipoproteins. METHODS: We used a fat tolerance test in 96 females and 62 males with blood sampled at 0, 2, and 4 h after a breakfast containing 26.3 g of fats. The postprandial triglyceride response was used to classify the individuals in apparently fat-tolerant and apparently fat-intolerant participants. RESULTS: The intolerant individuals were found to have at 0 h significantly higher body mass index, plasma triglycerides, remnant cholesterol, VLDL cholesterol, and LDL cholesterol and lower apolipoprotein (apo) AI and HDL cholesterol than the tolerant individuals. More than 70% of the variability (r2) of the postprandial response in tolerant and intolerant individuals measured as area under the curve or, at a single point at 4 h after the oral fat load, was linearly correlated with 0-h triglycerides (P < 0001). Fasting lipoprotein parameters, proposed to be markers of cardiovascular risk, as the ratios apo B/apo AI, total cholesterol/HDL cholesterol, and triglycerides/HDL cholesterol, were increased in the intolerant individuals. CONCLUSIONS: A simplified oral fat tolerance test, even when used in an apparently healthy, nonobese, normolipidemic cohort, detected that an increased postprandial triglycerides response was associated with augmented lipoprotein markers of increased cardiovascular risk.