Intestinal FABP, dietary fat and Type 2 diabetes in Mexican Americans

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Intestinal fatty acid binding protein 2 (FABP2) exhibits a functional single nucleotide polymorphism, Ala54Thr that result in two protein variants: FABP2 Ala54 and FABP2 Thr54. The FABP2 Thr54 variant exhibits a twofold increase in fatty acid binding compared to the FABP2 Ala54 normal increase fat absorption in the intestine, and carriers may show higher risk for insulin resistance and fasting blood glucose levels. The effect of the Ala54Thr SNP has not been well characterized in Mexican Americans and recent data suggest it is associated with type 2 diabetes (T2DM) in this ethnic group. Further, about 60% of Mexican American diabetic participants in our diabetes education program are FABP2 Thr54 carriers which provide an opportunity to assess if this high incidence may contribute to the severity of the disease. This study seeks to understand the effect of the FABP2 Thr54 in Mexican Americans with T2DM. Further, we will evaluate the effect of a lifestyle intervention designed to counteract the potential negative effect ofthe FABP2 54Thr variant in participants. Individuals shown to be threonine carriers (AT/TT genotypes) may interact differently with dietary fat and may provide an unique opportunity to develop successful personalized cultural competent lifestyle interventions to reduce the impact of the disease on Mexican Americans and other affected groups. Our central hypothesis is that Mexican Americans exhibit a threonine-carrier paradox modulated by the FABP2 Ala54Thr polymorphism. The three aims of the application are: Aim 1 is to determine the effect ofthe FABP2 Ala54Thr polymorphism on fasting blood glucose and lipid levels in MA with and without T2DM. Aim 2 is to determine the effect of the FABP2 Ala54Thr polymorphism on saturated fatty acid-induced lipotoxicity. Aim 3 is to determine the dietary fat and FABP2 Ala54Thr polymorphism interactions on fasting blood glucose and lipids levels in diabetic Mexican-Americans. The completion of these aims will increase our knowledge of the effects of this SNP in T2DM health disparities in Mexican Americans and may serve as foundation for the development of future personalized prevention diabetes education program targeting this ethnic group.