Abstract
Background
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.
Objective
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.
Design
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).
Results
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.
Conclusion
The novel finding of this study is the association of Thr54 allele with insulin resistance, leptin, and adiponectin levels in morbidly obese patients.
References
Rosenbaum M, Leibel RL, Hirsh J. Medical progress: obesity. New Engl J Med. 1997;337:396–407.
Scopinaro N, Adami GF, Marinari GM. Biliopancreatic diversión. World J Surg. 1998;22:936–46.
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.
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.
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)
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.
Kumada M, Kihara S, Sumitsuji S. Association of hypoadiponectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol. 2003;23:85–9.
Shimomoura I, Hammer RE, Ikemoto S. Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy. Nature. 1999;401:73–6.
Steppan CM, Bailey ST, Bhat S. The hormone resistin links obesity to diabetes. Nature. 2001;409:307–12.
Matsuzawa Y. Adipocytokines: emerging therapeutic targets. Curr Atheroscler Rep. 2005;7:58–62.
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.
Xenachis C, Samojlik E, Raghuwanshi MP, et al. Leptin, insulin and TNF-alpha in weight loss. J Endocrinol Invest. 2001;24:865–70.
Besnard P. Cellular and molecular aspects of fat metabolism in the small intestine. Proc Nutr Soc. 1996;5:19–37.
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.
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.
Duart MJ, Arroyo CO, Moreno JL. Validation of a insulin model for the reactions in RIA. Clin Chem Lab Med. 2002;40:1161–7.
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.
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.
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.
Suominen P. Evaluation of an enzyme immunometric assay to measure serum adiponectin concentrations. Clin Chem. 2004;50:219–21.
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.
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.
Pichard C, Slosman D, Hirschel B, et al. Bioimpedance analysis: an improved method for nutritional follow up. Clin Res. 1993;41:53.
Mataix J, Mañas M. Tablas de composición de alimentos españoles. Granada: University of Granada Ed; 2003.
Feurer ID, Mullen JL. Bedside measurement of resting energy expenditure and respiratory quotient via indirect calorimetry. Nutr Clin Pract. 1986;1:43–9.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
de Luis, D.A., Sagrado, M.G., Aller, R. et al. Ala54Thr Polymorphism of Fatty Acid Binding Protein 2, Role on Insulin Resistance and Cardiovascular Risk Factors in Presurgical Morbid Obesity Patients. OBES SURG 19, 1691–1696 (2009). https://doi.org/10.1007/s11695-009-9859-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11695-009-9859-x