Polimorfismo de la proteína ligante de ácidos grasos intestinal (FABP2), obesidad e insulina resistencia

Abstract

The genetic components of insulin-resistance, diabetes and obesity have been largely studied. These conditions are determined by multiple polygenic and environmental factors. Certain candidate genes, that have common functional variants in the general population, may be important determinants of inter-individual differences in the response to dietary changes. This review focuses in one of the major candidate genes, the gene encoding for the FABP2, an intracellular protein expressed only in the intestine, involved in the absorption and intracellular transport of dietary long chain fatty acids. Carriers of the Thr54 allele in FABP2 have a 2-fold greater affinity for long chain fatty acids than Ala54 carriers. The increased flux of dietary fatty acids (FA) into the circulation, among carriers of FABP2 Ala54Thr, supports a role of the polymorphism of this allele in the etiology of metabolic disorders. The frequencies of the polymorphism in different populations fluctuate between 18% and 40%. FABP2 Ala54Thr variant has been associated with an increased fasting insulin concentration, fasting fatty acid oxidation and reduced glucose uptake. This evidence, although not conclusive, sustains an association between FABP-2 genotype and metabolic abnormalities.

The A54T polymorphism in the FABP2 gene and its relationship with obesity

“…In Latin America, the genotypic frequency of the Ala54Thr variant is equally variable according to the population studied, as it is in the rest of the world. For example, in Chilean aboriginal populations, an allele frequency of 18.2 % in Aymaras and 31.9 % in Mapuches has been found (16). Similarly, in Argentina, a recent study revealed an allelic frequency of 0.277 (95 % confidence limits 0.234-0.323) and genotypic frequencies of 40 % for heterozygous and 7.42 % for homozygous (17).…”

“…The exposure proportion between cases was calculated at a 30 % level, OR detection limits of 4 and a case-control ratio of 1:3. The assigned value for was assumed by the literature review, which reflects similar data as used here (8). For calculation procedure, the program Epidat (4.2 version for Windows 64 bits) was used, obtaining a sample size of 144 individuals.…”

“…Phenotypic features in lipidic profile and both fasting and postprandial glycemic patterns associated with the A54T are different, maybe due to several factors like methodological or genetic/environmental interactions, two relevant points to consider when studying the causes of obesity and overweight (7). In this research, sequence polymorphism A54T in exon 2 of FABP2 was studied because of the scarce information regarding neither the prevalence nor the association with obesity, and possible confounder effect of other cardiovascular risk variables (16,17).…”

Síndrome metabólico: Bases clínicas y fisiopatológicas para un enfoque terapéutico racional

“…El polimorfismo de la "Fatty Acid Binding Protein 2" (FABP2) es uno de los genes candidatos que han sido asociados con RI y obesidad 36 . Esta proteína participa en el transporte de ácidos grasos de cadena larga a nivel intestinal.…”