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Gene Review

FABP2  -  fatty acid binding protein 2, intestinal

Homo sapiens

Synonyms: FABPI, Fatty acid-binding protein 2, Fatty acid-binding protein, intestinal, I-FABP, Intestinal-type fatty acid-binding protein
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Disease relevance of FABP2

  • These results suggest that in African-Americans, these variants in the IRS-1 and FABP2 genes are not associated with the risk of type 2 diabetes, severe obesity, or marked hyperinsulinemia, but that their independent and joint effects may be associated with small increases in BMI [1].
  • It is proposed that, in the absence of confounding factors such as environmental and genetic variables, the FABP2 polymorphism has an important effect on postprandial lipids in vivo, potentially influencing plasma levels of lipids and atherogenesis [2].
  • Our objectives were to determine whether Ala54Thr FABP2 and G-493T MTP polymorphisms are associated with increased risks of insulin resistance syndrome (IRS) in youth and/or modify the expression of accompanying dyslipidemia [3].
  • Our study suggests that the effects of FABP2 allelic variations on lipid traits are context dependent, indicating that this variant may play an important role in cardiovascular pathogenesis in the presence of IRS or hypertriglyceridemia [3].
  • Moreover, there was no significant relationship between FABP2 alleles and lipoprotein diameter or the prevalence of coronary heart disease in both genders [4].

Psychiatry related information on FABP2


High impact information on FABP2

  • Since the FABP2 threonine-encoding allele was found to be associated with insulin resistance and increased fat oxidation in vivo, we further analyzed the FABP2 gene products for potential functional differences [6].
  • The intestinal fatty acid binding protein locus (FABP2) was investigated as a possible genetic factor in determining insulin action in the Pima Indian population [6].
  • A polymorphism at codon 54 of FABP2 was identified that results in an alanine-encoding allele (frequency 0.71) and a threonine-encoding allele (frequency 0.29) [6].
  • Experimental studies have suggested rat intestinal fatty acid-binding protein (I-FABP) as a serum marker reflecting bowel ischemia; the present study evaluates the human homologue (human I-FABP) as a serum marker for the diagnosis of acute ischemic diseases of the bowel [7].
  • All 5 patients with mesenteric infarction showed I-FABP levels of > 100 ng/mL [7].

Chemical compound and disease context of FABP2


Biological context of FABP2


Anatomical context of FABP2

  • We examined the association between the Ala(54)Thr variant in the FABP2 gene and levels of visceral (VAT) and sc (SAAT) abdominal fat in a group of 223 premenopausal African-American (n = 103) and Caucasian (n = 120) women [12].
  • FABP2, the intestinal-type FABP, is expressed exclusively in enterocytes in the small intestine [14].
  • In conclusion, Thr54 allele of FABP2 has associations with lower adjusted resting metabolic rate, resistance in reducing visceral white adipose tissue (WAT) and early onset of obesity in Japanese obese women [15].
  • In subjects with coronary artery disease (CAD+), the prevalence of FABP-2 54TT genotype was higher (16.5% versus 5.2%) and that of ABCA1 219RK and KK genotypes lower (33.0% versus 51.5%) than in subjects with no CAD [16].
  • Moreover, it appears that the Ala to Thr substitution at residue 54 of the human IFABP does not alter the fundamental mechanism of ligand transfer to membranes, but nevertheless causes a consistent decrease in the rate of transfer [17].

Associations of FABP2 with chemical compounds

  • Our data clearly document that the A54T polymorphism of FABP2 specifically influences small intestinal lipid absorption without modifying glucose uptake or metabolism [2].
  • FABP2 genotype was not associated with fasting or postprandial lipemia test triacylglycerol or free fatty acids (P >/= 0.22 for all), but postprandial lipid oxidation rates were higher (P = 0.01), which suggests that fat absorption is higher in Thr54 carriers than in Ala54 homozygotes [18].
  • In summary, we have confirmed the association of the FABP2 T54 allele with increased concentrations of cholesterol and triglycerides in genotype-discordant sibling pairs [13].
  • Among the metabolic components of IRS, only triglyceride (TG) displayed an interaction with FABP2 polymorphism: compared with Thr/Ala and Ala/Ala, the Thr/Thr genotype was associated with a steeper increase in TC, LDL-C, and apoB parallel to TG concentrations (P <0.001) [3].
  • CONCLUSIONS: An adverse combination of common alleles of the FABP-2, APOE, and PPARgamma genes in women increases their TG concentrations to values comparable to those seen in men [19].

Physical interactions of FABP2


Regulatory relationships of FABP2


Other interactions of FABP2

  • Allelic frequencies in 70 controls and 110 patients with diabetes from the Chennai Urban Population Study were 52.9% for FABP2 Thr54, 73.0% for APOC3 -482T, and 80.2% for APOC3 -455C [25].
  • Also, very modest genotype-phenotype associations were observed between APOE genotype (P = 0.016) and plasma low-density lipoprotein cholesterol concentration and between FABP2 genotype and plasma 2-h postprandial, glucose concentration (P = 0.048) [26].
  • In women only, both GNB3 825C>T and FABP2 A54T genotypes were significantly associated with HTGW (OR 2.02, 95% CI 1.01, 4.05 and OR 1.95, 95% CI 1.01, 3.74, respectively) [27].
  • Polymorphism of the fatty acid-binding protein 2 (FABP2) gene has been shown to affect the affinity of intestinal FABP for fatty acids [28].
  • Most NIDDM result from polygenic heredity, and susceptibility genes conducive to increased receptivity to deleterious environmental influences are now under investigation, such as beta 3 adrenergic receptor, FABP2 and OB [29].

Analytical, diagnostic and therapeutic context of FABP2

  • OBJECTIVE: We tested the hypothesis that, in sedentary nondiabetic subjects following a low-fat diet, Thr54 FABP2 carriers have lower glucoregulatory function, greater postprandial lipemia, and greater lipid oxidation rates than do their Ala54 FABP2-homozygous counterparts [18].
  • DISCUSSION: Serum I-FABP levels do not predict clinical intestinal allograft rejection [30].
  • MATERIALS AND METHODS: I-FABP was repetitively measured in nine intestinal transplant recipients and correlated with findings of surveillance endoscopy [30].
  • DESIGN AND METHODS: I-FABP and L-FABP were measured with specific immunoassays in autopsy samples of the intestine (duodenum, jejunum, ileum and colon) of 23 subjects and in plasma samples from patients (n = 51) with intestinal and/or hepatic disease [31].
  • No significant association was obtained between the polymorphism of the FABP2 gene and body mass index [32].


  1. Variants of the insulin receptor substrate-1 and fatty acid binding protein 2 genes and the risk of type 2 diabetes, obesity, and hyperinsulinemia in African-Americans: the Atherosclerosis Risk in Communities Study. Lei, H.H., Coresh, J., Shuldiner, A.R., Boerwinkle, E., Brancati, F.L. Diabetes (1999) [Pubmed]
  2. The polymorphism at codon 54 of the FABP2 gene increases fat absorption in human intestinal explants. Levy, E., Ménard, D., Delvin, E., Stan, S., Mitchell, G., Lambert, M., Ziv, E., Feoli-Fonseca, J.C., Seidman, E. J. Biol. Chem. (2001) [Pubmed]
  3. Intestinal fatty acid binding protein and microsomal triglyceride transfer protein polymorphisms in French-Canadian youth. Stan, S., Lambert, M., Delvin, E., Paradis, G., O'loughlin, J., Hanley, J.A., Levy, E. J. Lipid Res. (2005) [Pubmed]
  4. Association of the A/T54 polymorphism in the intestinal fatty acid binding protein with variations in plasma lipids in the Framingham Offspring Study. Galluzzi, J.R., Cupples, L.A., Otvos, J.D., Wilson, P.W., Schaefer, E.J., Ordovas, J.M. Atherosclerosis (2001) [Pubmed]
  5. FABP2 genotype is associated with insulin sensitivity in older women. Brown, M.D., Shuldiner, A.R., Ferrell, R.E., Weiss, E.P., Korytkowski, M.T., Zmuda, J.M., McCole, S.D., Moore, G.E., Hagberg, J.M. Metab. Clin. Exp. (2001) [Pubmed]
  6. An amino acid substitution in the human intestinal fatty acid binding protein is associated with increased fatty acid binding, increased fat oxidation, and insulin resistance. Baier, L.J., Sacchettini, J.C., Knowler, W.C., Eads, J., Paolisso, G., Tataranni, P.A., Mochizuki, H., Bennett, P.H., Bogardus, C., Prochazka, M. J. Clin. Invest. (1995) [Pubmed]
  7. Intestinal fatty acid-binding protein is a useful diagnostic marker for mesenteric infarction in humans. Kanda, T., Fujii, H., Tani, T., Murakami, H., Suda, T., Sakai, Y., Ono, T., Hatakeyama, K. Gastroenterology (1996) [Pubmed]
  8. Obesity, Type II diabetes and the Ala54Thr polymorphism of fatty acid binding protein 2 in the Tongan population. Duarte, N.L., Colagiuri, S., Palu, T., Wang, X.L., Wilcken, D.E. Mol. Genet. Metab. (2003) [Pubmed]
  9. Postprandial lipemia in subjects with the threonine 54 variant of the fatty acid-binding protein 2 gene is dependent on the type of fat ingested. Dworatzek, P.D., Hegele, R.A., Wolever, T.M. Am. J. Clin. Nutr. (2004) [Pubmed]
  10. Variation of the fatty acid binding protein 2 gene is not associated with obesity and insulin resistance in Japanese subjects. Hayakawa, T., Nagai, Y., Nohara, E., Yamashita, H., Takamura, T., Abe, T., Nomura, G., Kobayashi, K. Metab. Clin. Exp. (1999) [Pubmed]
  11. Trinucleotide repeat polymorphism at the human intestinal fatty acid binding protein gene (FABP2). Polymeropoulos, M.H., Rath, D.S., Xiao, H., Merril, C.R. Nucleic Acids Res. (1990) [Pubmed]
  12. Association of the intestinal fatty acid-binding protein Ala54Thr polymorphism and abdominal adipose tissue in African-American and Caucasian women. Lara-Castro, C., Hunter, G.R., Lovejoy, J.C., Gower, B.A., Fernández, J.R. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  13. The T 54 allele of the intestinal fatty acid-binding protein 2 is associated with a parental history of stroke. Carlsson, M., Orho-Melander, M., Hedenbro, J., Almgren, P., Groop, L.C. J. Clin. Endocrinol. Metab. (2000) [Pubmed]
  14. Variation in the FABP2 promoter alters transcriptional activity and is associated with body composition and plasma lipid levels. Damcott, C.M., Feingold, E., Moffett, S.P., Barmada, M.M., Marshall, J.A., Hamman, R.F., Ferrell, R.E. Hum. Genet. (2003) [Pubmed]
  15. Thr54 allele of the FABP2 gene affects resting metabolic rate and visceral obesity. Takakura, Y., Yoshioka, K., Umekawa, T., Kogure, A., Toda, H., Yoshikawa, T., Yoshida, T. Diabetes Res. Clin. Pract. (2005) [Pubmed]
  16. Genetic polymorphisms affecting the phenotypic expression of familial hypercholesterolemia. Bertolini, S., Pisciotta, L., Di Scala, L., Langheim, S., Bellocchio, A., Masturzo, P., Cantafora, A., Martini, S., Averna, M., Pes, G., Stefanutti, C., Calandra, S. Atherosclerosis (2004) [Pubmed]
  17. Similar mechanisms of fatty acid transfer from human anal rodent fatty acid-binding proteins to membranes: liver, intestine, heart muscle, and adipose tissue FABPs. Storch, J., Veerkamp, J.H., Hsu, K.T. Mol. Cell. Biochem. (2002) [Pubmed]
  18. FABP2 Ala54Thr genotype is associated with glucoregulatory function and lipid oxidation after a high-fat meal in sedentary nondiabetic men and women. Weiss, E.P., Brandauer, J., Kulaputana, O., Ghiu, I.A., Wohn, C.R., Phares, D.A., Shuldiner, A.R., Hagberg, J.M. Am. J. Clin. Nutr. (2007) [Pubmed]
  19. Additive effects of the PPARgamma, APOE, and FABP-2 genes in increasing daylong triglycerides of normolipidemic women to concentrations comparable to those in men. Ribalta, J., Halkes, C.J., Salazar, J., Masana, L., Cabezas, M.C. Clin. Chem. (2005) [Pubmed]
  20. Time-resolved fluorescence of intestinal and liver fatty acid binding proteins: role of fatty acyl CoA and fatty acid. Frolov, A., Schroeder, F. Biochemistry (1997) [Pubmed]
  21. PYY-mediated fatty acid induced intestinal differentiation. Aponte, G.W. Peptides (2002) [Pubmed]
  22. The human intestinal fatty acid binding protein (hFABP2) gene is regulated by HNF-4alpha. Klapper, M., Böhme, M., Nitz, I., Döring, F. Biochem. Biophys. Res. Commun. (2007) [Pubmed]
  23. Modulation of intestinal and liver fatty acid-binding proteins in Caco-2 cells by lipids, hormones and cytokines. Dubé, N., Delvin, E., Yotov, W., Garofalo, C., Bendayan, M., Veerkamp, J.H., Levy, E. J. Cell. Biochem. (2001) [Pubmed]
  24. Postprandial responses of individual fatty acids in subjects homozygous for the threonine- or alanine-encoding allele in codon 54 of the intestinal fatty acid binding protein 2 gene. Agren, J.J., Vidgren, H.M., Valve, R.S., Laakso, M., Uusitupa, M.I. Am. J. Clin. Nutr. (2001) [Pubmed]
  25. Polymorphisms in the fatty acid-binding protein 2 and apolipoprotein C-III genes are associated with the metabolic syndrome and dyslipidemia in a South Indian population. Guettier, J.M., Georgopoulos, A., Tsai, M.Y., Radha, V., Shanthirani, S., Deepa, R., Gross, M., Rao, G., Mohan, V. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  26. Are Canadian Inuit at increased genetic risk for coronary heart disease? Hegele, R.A., Young, T.K., Connelly, P.W. J. Mol. Med. (1997) [Pubmed]
  27. Clinical and genetic associations with hypertriglyceridemic waist in a Canadian aboriginal population. Pollex, R.L., Hanley, A.J., Zinman, B., Harris, S.B., Hegele, R.A. International journal of obesity (2005) (2006) [Pubmed]
  28. Postprandial lipemic response is modified by the polymorphism at codon 54 of the fatty acid-binding protein 2 gene. Agren, J.J., Valve, R., Vidgren, H., Laakso, M., Uusitupa, M. Arterioscler. Thromb. Vasc. Biol. (1998) [Pubmed]
  29. Diabetes: from phenotypes to genotypes. Guillausseau, P.J., Tielmans, D., Virally-Monod, M., Assayag, M. Diabetes Metab. (1997) [Pubmed]
  30. Lack of utility of intestinal fatty acid binding protein levels in predicting intestinal allograft rejection. Kaufman, S.S., Lyden, E.R., Marks, W.H., Lieberman, J., Sudan, D.L., Fox, I.F., Shaw, B.W., Horslen, S.P., Langnas, A.N. Transplantation (2001) [Pubmed]
  31. Intestinal-type and liver-type fatty acid-binding protein in the intestine. Tissue distribution and clinical utility. Pelsers, M.M., Namiot, Z., Kisielewski, W., Namiot, A., Januszkiewicz, M., Hermens, W.T., Glatz, J.F. Clin. Biochem. (2003) [Pubmed]
  32. Association between Ala54Thr substitution of the fatty acid-binding protein 2 gene with insulin resistance and intra-abdominal fat thickness in Japanese men. Yamada, K., Yuan, X., Ishiyama, S., Koyama, K., Ichikawa, F., Koyanagi, A., Koyama, W., Nonaka, K. Diabetologia (1997) [Pubmed]
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