Obesity Surgery

, Volume 19, Issue 12, pp 1691–1696 | Cite as

Ala54Thr Polymorphism of Fatty Acid Binding Protein 2, Role on Insulin Resistance and Cardiovascular Risk Factors in Presurgical Morbid Obesity Patients

  • D. A. de LuisEmail author
  • M. Gonzalez Sagrado
  • R. Aller
  • O. Izaola
  • R. Conde
  • Enrique Romero
Clinical Report



A transition G to A at codon 54 of fatty acid binding protein 2 (FABP2) results in an amino acid substitution (ala 54 to Thr 54). This polymorphism was associated with insulin resistance in some populations.


The aim of our study was to investigate the influence of Thr54 polymorphism in the FABP2 gene on obesity anthropometric parameters, cardiovascular risk factors, and adipocytokines in patients with presurgical morbid obesity.


A population of 55 morbid obese patients was enrolled. An indirect calorimetry, tetrapolar electrical bioimpedance, blood pressure, a serial assessment of nutritional intake with 3 days of written food records, and biochemical analysis (lipid profile, adipocytokines, insulin, C-reactive protein, and lipoprotein-a) were performed. The statistical analysis was performed for the combined Ala54/Thr54 and Thr54/Thr54 as a mutant-type group and wild-type group (Ala54/Ala54).


Twenty nine (52.7%) had the genotype Ala54/Ala54 (wild-type group) and 26 (47.3%) patients had the genotype Ala54/Thr54 (24 patients, 43.7%) or Thr54/Thr54 (two patients, 3.6%; mutant-type group). Insulin (22.4 ± 16.8 vs. 26.1 ± 17.1 mg/dl; p = 0.04) and homeostasis model assessment (6.1 ± 2.1 vs. 6.7 ± 4.5; p = 0.04) levels were higher in mutant-type group than wild-type group. In mutant-type group, leptin levels (134.8 ± 83 vs. 206.5 ± 76 ng/ml; p = 0.03) were higher than wild-type group. Moreover, adiponectin levels (80.9 ± 39.6 vs. 23.9 ± 13.8 ng/ml; p = 0.02) were higher in wild-type group than mutant-type group.


The novel finding of this study is the association of Thr54 allele with insulin resistance, leptin, and adiponectin levels in morbidly obese patients.


Adipokines Cardiovascular risk factors FABP2 Presurgical morbid obesity Polymorphism 


  1. 1.
    Rosenbaum M, Leibel RL, Hirsh J. Medical progress: obesity. New Engl J Med. 1997;337:396–407.CrossRefGoogle Scholar
  2. 2.
    Scopinaro N, Adami GF, Marinari GM. Biliopancreatic diversión. World J Surg. 1998;22:936–46.CrossRefGoogle Scholar
  3. 3.
    de Luis DA, Pacheco D, Aller R, et al. Influence of -55CT polymorphism of UCP3 gene on surgical results of biliopancreatic diversion. Obes Surg. 2008;. doi: 10.1007/s11695-008-9510-2.CrossRefGoogle Scholar
  4. 4.
    de Luis DA, González Sagrado M, Izaola O, et al. Influence of Ala54Thr polymorphism of fatty acid-binding protein-2 on clinical results of biliopancreatic diversion. Nutrition. 2008;24:300–4.CrossRefGoogle Scholar
  5. 5.
    de Luis DA, Pacheco D, Aller R, et al. Influence of G308 polymorphism of Tumor necrosis alpha gene on surgical results of biliopancreatic diversion. Obes Surg 2008 (in press)Google Scholar
  6. 6.
    Matsuda M, Shimomura I, Sata M. Role of adiponectin in preventing vascular stenosis. The missing link of adipo-vascular axis. J Biol Chem. 2002;277:37487–91.CrossRefGoogle Scholar
  7. 7.
    Kumada M, Kihara S, Sumitsuji S. Association of hypoadiponectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol. 2003;23:85–9.CrossRefGoogle Scholar
  8. 8.
    Shimomoura I, Hammer RE, Ikemoto S. Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy. Nature. 1999;401:73–6.CrossRefGoogle Scholar
  9. 9.
    Steppan CM, Bailey ST, Bhat S. The hormone resistin links obesity to diabetes. Nature. 2001;409:307–12.CrossRefGoogle Scholar
  10. 10.
    Matsuzawa Y. Adipocytokines: emerging therapeutic targets. Curr Atheroscler Rep. 2005;7:58–62.CrossRefGoogle Scholar
  11. 11.
    Okasaki T, Himeno E, Nanri H, et al. Effects of mild aerobic exercise and a mild hypocaloric diet on plasma leptin in sedentary women. Clin Exp Pharmacol. 1999;26:415–20.CrossRefGoogle Scholar
  12. 12.
    Xenachis C, Samojlik E, Raghuwanshi MP, et al. Leptin, insulin and TNF-alpha in weight loss. J Endocrinol Invest. 2001;24:865–70.CrossRefGoogle Scholar
  13. 13.
    Besnard P. Cellular and molecular aspects of fat metabolism in the small intestine. Proc Nutr Soc. 1996;5:19–37.CrossRefGoogle Scholar
  14. 14.
    Baier LJ, Sacchettini JC, Knowler WC. 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. J Clin Invest. 1995;95:1281–7.CrossRefGoogle Scholar
  15. 15.
    Albala C, Santos JL, Viallaroel AC, et al. Intestinal FABP2 A54T polymorphism: association with insulin resistance and obesity in women. Obes Res. 2004;12:340–5.CrossRefGoogle Scholar
  16. 16.
    Duart MJ, Arroyo CO, Moreno JL. Validation of a insulin model for the reactions in RIA. Clin Chem Lab Med. 2002;40:1161–7.CrossRefGoogle Scholar
  17. 17.
    Mathews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and beta cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–4.CrossRefGoogle Scholar
  18. 18.
    Pfutzner A, Langefeld M, Kunt T, et al. Evaluation of human resistin assays with serum from patients with type 2 diabetes and different degrees of insulin resistance. Clin Lab. 2003;49:571–6.PubMedGoogle Scholar
  19. 19.
    Meier U, Gressner M. Endocrine regulation of energy metabolism: review of pathobiochemical and clinical chemical aspects of leptin, ghrelin, adiponectin, and resistin. Clin Chem. 2004;50:1511–25.CrossRefGoogle Scholar
  20. 20.
    Suominen P. Evaluation of an enzyme immunometric assay to measure serum adiponectin concentrations. Clin Chem. 2004;50:219–21.CrossRefGoogle Scholar
  21. 21.
    Lubrano V, Cocci F, Battaglia D, et al. Usefulness of high-sensitivity IL6 measurement for clinical characterization of patients with coronary artery disease. J Clin Lab Anal. 2005;19:110–4.CrossRefGoogle Scholar
  22. 22.
    Khan SS, Smith MS, Reda D, et al. Multiplex bead array assays for detection of soluble cytokines: comparisons of sensitivity and quantitative values among kits from multiple manufactures. Cytometry B Clin Cytom. 2004;61:35–9.CrossRefGoogle Scholar
  23. 23.
    Pichard C, Slosman D, Hirschel B, et al. Bioimpedance analysis: an improved method for nutritional follow up. Clin Res. 1993;41:53.Google Scholar
  24. 24.
    Mataix J, Mañas M. Tablas de composición de alimentos españoles. Granada: University of Granada Ed; 2003.Google Scholar
  25. 25.
    Feurer ID, Mullen JL. Bedside measurement of resting energy expenditure and respiratory quotient via indirect calorimetry. Nutr Clin Pract. 1986;1:43–9.CrossRefGoogle Scholar
  26. 26.
    Sipilainen R, Uusitupa M, Heikkinen S, et al. Variants in the human intestinal fatty acid binding protein 2 gene in obese subjects. J Clin Endocrinol Metab. 1997;82:2629–32.CrossRefGoogle Scholar
  27. 27.
    Prochazka M, Lillioja S, Tait JF. Linkage of chromosomal markers on 4q with a putative gene determining maximal insulin action in Pima Indians. Diabetes. 1993;42:514–9.CrossRefGoogle Scholar
  28. 28.
    Mitchell BD, Kammerer CM, O’Connell P. Evidence for linkage of postchallenge insulin levels with intestinal fatty acid-binding protein (FABP-2) in Mexican Americans. Diabetes. 1995;44:1046–53.CrossRefGoogle Scholar
  29. 29.
    Chiu KC, Chuang LM, Yoon C. The A54T polymorphism at the intestinal fatty acid binding protein 2 is associated with insulin resistance in glucose tolerant Caucasians. BMC Genet. 2001;2:7–13.CrossRefGoogle Scholar
  30. 30.
    Yamada K, Yuan X, Ishimayama S. Association between Ala 54Thr substitution of the fatty acid binding protein 2 gene with insulin resistance and intra abdominal fat thickness in Japanese men. Diabetologia. 1997;40:706–10.CrossRefGoogle Scholar
  31. 31.
    Kim CH, Yun SK, Byun DW. Codon 4 polymorphism of the fatty acid binding protein 2 gene is associated with increased fat oxidation and hyperinsulinemia but not with intestinal fatty acid absorption in Korean Men. Metabolism. 2001;50:473–6.CrossRefGoogle Scholar
  32. 32.
    de Luis DA, Sagrado MG, Aler R, et al. Influence of Ala54Thr polymorphism of fatty acid binding protein 2 on obesity and cardiovascular risk factors. Horm Metab Res. 2007;39:380–4.Google Scholar
  33. 33.
    Georgopoulos A, Aras O, Tsai MY. Codon 54 polymorphism of the fatty acid binding protein 2 gene is associated with elevation of fasting and postprandial triglyceride in type 2 diabetes. J Clin Endocr Metab. 2000;85:3155–60.PubMedGoogle Scholar
  34. 34.
    Georgopoulos A, Aras O, Noutsou M, et al. Unlike type 2 diabetes, type 1 does not interact with the codon 54 polymorphism of the fatty acid binding protein 2 gene. J Clin Endocr. 2002;87:3735–9.CrossRefGoogle Scholar
  35. 35.
    Carlsson M, Orho Melander M, Hedenbro J, et al. The T54 allele of the intestinal fatty acid-binding protein 2 is associated with parenteral history of stroke. J Clin Endocr Metab. 2000;85:2801–4.PubMedGoogle Scholar
  36. 36.
    Duarte NL, Colagiuri S, Palu T, et al. Obesity, type II diabetes and the Ala54 Thr polymorphism of fatty acid binding protein 2 in the Tongan population. Mol Genet Metab. 2003;79:183–9.CrossRefGoogle Scholar
  37. 37.
    de Luis DA, Aller R, Izaola O, et al. Modulation of the response to a lifestyle modification in obese patients by ala54thr polymorphism of the fatty acid-binding protein 2 gene. Ann Nutr Metab. 2006;50:354–60.CrossRefGoogle Scholar
  38. 38.
    de Luis DA, Aller R, Izaola O, et al. Influence of ALA54THR polymorphism of FABP-2 on weight loss and insulin levels secondary to two hypocaloric diets: a randomized clinical trial. Diab Res Clin Pract. 2008;82:113–8. doi: 10.1016/j.diabres.2008.07.005.CrossRefGoogle Scholar

Copyright information

© Springer Science + Business Media, LLC 2009

Authors and Affiliations

  • D. A. de Luis
    • 1
    • 2
    Email author
  • M. Gonzalez Sagrado
    • 1
  • R. Aller
    • 1
  • O. Izaola
    • 1
  • R. Conde
    • 1
  • Enrique Romero
    • 1
  1. 1.Institute of Endocrinology and Nutrition, Medicine School and Unit of Investigation, Hospital Rio HortegaUniversity of ValladolidValladolidSpain
  2. 2.Institute of Endocrinology and Nutrition, Medicine SchoolValladolid UniversityValladolidSpain

Personalised recommendations