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Horm Metab Res 2007; 39(11): 830-834
DOI: 10.1055/s-2007-991179
Humans, Clinical

© Georg Thieme Verlag KG Stuttgart · New York

Influence of ALA54THR Polymorphism of Fatty Acid-binding Protein 2 on Obesity and Cardiovascular Risk Factors

D. A. de Luis 1 , M. G. Sagrado 1 , R. Aller 1 , O. Izaola 1 , R. Conde 1
  • 1Institute of Endocrinology and Nutrition, Medicine School and Unit of Investigation, Hospital Rio Hortega, University of Valladolid, Valladolid, Spain
Further Information

Publication History

received 22.01.2007

accepted 19.03.2007

Publication Date:
09 November 2007 (online)

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Abstract

A transition of G to A at codon 54 of FABP2 results in an amino acid substitution (Ala54 to Thr54). This polymorphism was associated with some cardiovascular risk factors. The aim of our study was to investigate the influence of Thr54 polymorphism in the FABP2 gene on obesity anthropometric parameters and cardiovascular risk factors. A population of 226 obesity (body mass index >30) nondiabetic outpatients were analyzed. 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, CRP, and lipoprotein-a) were performed. The statistical analysis was performed for the combined Ala54/Thr54 and Thr54/Thr54 as a mutant group and wild type Ala54/Ala54 as a second group. Two-hundred and twenty-six patients gave informed consent and were enrolled in the study. The mean age was 44.2±16 years and the mean BMI 35.1±5.1, with 63 males (28.3%) and 163 females (71.7%). One-hundred and thirteen patients (50%) had the genotype Ala54/Ala54 (wild group) and 113 (50%) patients had the genotype Ala54/Thr54 (91 patients, 40.2%) or Thr54/Thr54 (22 patients, 9.8%) (mutant group). The ANOVA analysis of the three groups (Ala54/Thr54, Thr54/Thr54 and Ala54/Ala54) shows a higher levels of fat mass in Thr54/Thr54 group (45.6±14.6 kg) than Ala54/Ala54 (37.5±11.2 kg: p<0.05), without differences with Ala54/Thr54 group (41.2±13.5 kg). CRP, IL-6, and lipoprotein-a were higher in mutant group (Ala54/Thr54, Thr54/Thr54) than in wild group (Ala54/Ala54). The novel finding of this study is the association of the Thr54/Ala54 and Thr54/Thr54 FABP2 phenotypes with higher levels of C reactive protein, IL6, and lipoprotein-a. Further studies are needed to explain the role of this polymorphism in different populations.

Key words

adipokines - FABP2 - obesity - polymorphism - risk factors

References

  • 1 Aranceta J, Perez Rodrigo C, Serra Majem L. Prevalencia de la obesidad en España: estudio SEEDO 97.  Med Clin (Barc). 1998;  111 441-445
    PubMedGoogle Scholar
  • 2 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 37487-37491
    CrossrefPubMedGoogle Scholar
  • 3 Kumada M, Kihara S, Sumitsuji S. Association of hypoadiponectinemia with coronary artery disease in men.  Arterioscler Thromb Vasc Biol. 2003;  23 85-89
    CrossrefPubMedGoogle Scholar
  • 4 Shimomoura I, Hammer RE, Ikemoto S. Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy.  Nature. 1999;  401 73-76
    CrossrefPubMedGoogle Scholar
  • 5 Steppan CM, Bailey ST, Bhat S. The hormone resistin links obesity to diabetes.  Nature. 2001;  409 307-312
    CrossrefPubMedGoogle Scholar
  • 6 Matsuzawa Y. Adipocytokines: Emerging therapeutic targets.  Curr Atheroscler Rep. 2005;  7 58-62
    CrossrefPubMedGoogle Scholar
  • 7 Okasaki T, Himeno E, Nanri H, Ogata H, Ikeda M. Effects of mild aerobic exercise and a mild hypocaloric diet on plasma leptin in sedentary women.  Clin Exp Pharmacol. 1999;  26 415-420
    PubMedGoogle Scholar
  • 8 Xenachis C, Samojlik E, Raghuwanshi MP, Kirschner MA. Leptin, in-sulin and TNF-alpha in weight loss.  J Endocrinol Invest. 2001;  24 865-870
    PubMedGoogle Scholar
  • 9 Besnard P. Cellular and molecular aspects of fat metabolism in the small intestine.  Proc Nutr Soc. 1996;  5 19-37
    PubMedGoogle Scholar
  • 10 Nieuwenhoven FA Van, Vusse GJ Van der, Glatz JFC. Membrane associated and cytoplasmatic fatty acid binding proteins.  Lipids. 1996;  30 S223-S227
    PubMedGoogle Scholar
  • 11 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 1281-1287
    PubMedGoogle Scholar
  • 12 Albala C, Santos JL, Viallaroel AC, Lera L, Liberman C. Intestinal FABP2 A54 T polymorphism: Association with insulin resistance and obesity in women.  Obes Res. 2004;  12 340-345
    PubMedGoogle Scholar
  • 13 Duart MJ, Arroyo CO, Moreno JL. Validation of a insulin model for the reactions in RIA.  Clin Chem Lab Med. 2002;  40 1161-1167
    CrossrefPubMedGoogle Scholar
  • 14 Mathews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF. Homesotasis model assessment: insulin resistance and beta cell function from fasting plasma glucose and insulin concentrations in man.  Diabetologia. 1985;  28 412-414
    Google Scholar
  • 15 Pfutzner A, Langefeld M, Kunt T, Lobig M. Evaluation of human resistin assays with serum from patients with type 2 diabetes and different degrees of insulin resistance.  Clin Lab. 2003;  49 571-576
    PubMedGoogle Scholar
  • 16 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 1511-1525
    CrossrefPubMedGoogle Scholar
  • 17 Suominen P. Evaluation of an enzyme immunometric assay to measure serum adiponectin concentrations.  Clin Chem. 2004;  50 219-221
    CrossrefPubMedGoogle Scholar
  • 18 Lubrano V, Cocci F, Battaglia D, Papa A. Usefulness of high sensitivity IL6 measurement for clinical characterization of patients with coronary artery disease.  J Clin Lab Anal. 2005;  19 110-114
    CrossrefPubMedGoogle Scholar
  • 19 Khan SS, Smith MS, Reda D, Suffredini AF, Mac Coy JP. Multiplex bead array assays for detection of soluble cytokines: comparisons of sensitivity and quantitative values among kits from multiple manufactures.  Cytom B Clin Cytom. 2004;  61 35-39
    PubMedGoogle Scholar
  • 20 Feurer ID, Mullen JL. Bedside measurement of resting energy expenditure and respiratory quotient via indirect calorimetry.  Nutr Clin Pract. 1986;  1 43-49
    PubMedGoogle Scholar
  • 21 Pichard C, Slosman D, Hirschel B, Kyle U. Bioimpedance analysis in AIDS patients: an improved method for nutritional follow up.  Clin Res. 1993;  41 53
    PubMedGoogle Scholar
  • 22 Mataix J, Mañas M. Tablas de composición de alimentos españoles. University of Granada 1998
  • 23 Sipilainen R, Uusitupa M, Heikkinen S, Rissanen A, Laakso M. Variants in the human intestinal fatty acid binding protein 2 gene in obese subjects.  J Clin Endocrinol Metab. 1997;  82 2629-2632
    CrossrefPubMedGoogle Scholar
  • 24 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;  42 514-519
    PubMedGoogle Scholar
  • 25 Mitchell BD, Kammerer CM, O’Connell P. Evidence for linkage of postchallende insulin levels with intestinal fatty acid-binding protein (FABP-2) in Mexican Americans.  Diabetes. 1995;  44 1046-1053
    CrossrefPubMedGoogle Scholar
  • 26 Chiu KC, Chuang LM, Yoon C. The A54 T polymorphism at the intestinal fatty acid binding protein 2 is associated with insulin resistance in glucose tolerant Caucasians.  BMC Genet. 2001;  2 7-13
    CrossrefPubMedGoogle Scholar
  • 27 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;  40 706-710
    CrossrefPubMedGoogle Scholar
  • 28 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;  50 473-476
    CrossrefPubMedGoogle Scholar
  • 29 Carlsson M, Orho Melander M, Hedenbro J, Alegren P, Groop LC. The T54 allele of the intestinal fatty acid-binding protein 2 is associated with parenteral history of stroke.  J Clin Endocrinol Metab. 2000;  85 2801-2804
    CrossrefPubMedGoogle Scholar
  • 30 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 Endocrinol Metab. 2000;  85 3155-3160
    CrossrefPubMedGoogle Scholar
  • 31 Georgopoulos A, Aras O, Noutsou M, Tsai MY. Unlike type 2 diabetes, type 1 does not interact with the codon 54 polymorphism of the fatty acid binding protein 2 gene.  J Clin Endocrinol. 2002;  87 3735-3739
    PubMedGoogle Scholar
  • 32 Stem MP, Mitchell DB, Baglero J, Reinhart L, Krammerer CM, Harrison CR. Evidence for a major gene type II diabetes and linkage analysis with selected candidates’ genes in Mexican Americans.  Diabetes. 1996;  45 563-568
    CrossrefPubMedGoogle Scholar
  • 33 Vionnet N, Hani EH, Leage S, Philippi A, Hager J, Varret M. et al . Genetics of NIDDM in France: studies with 19 candidate genes in affected sib pairs.  Diabetes. 1997;  46 1062-1068
    PubMedGoogle Scholar
  • 34 Duarte NL, Colagiuri S, Palu T, Wang XL, Wilcken DEL. Obesity, typeII diabetes and the Ala54 Thr polymorphism of fatty acid binding protein 2 in the Tongan population.  Mol Genet Metab. 2003;  79 183-189
    CrossrefPubMedGoogle Scholar
  • 35 Agren JJ, Vidgren HM, Valve RS, Laakso M, Uusitupa MI. 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.  Am J Clin Nutr. 2001;  73 31-35
    PubMedGoogle Scholar
  • 36 Li Y, Fisher E, Klapper M, Boening H, Pfeiffer A, Hampe J. et al . Association between functional FABP2 promoter haplotype and type 2 diabetes.  Horm Metab Res. 2006;  38 300-307
    Article in Thieme ConnectPubMedGoogle Scholar
  • 37 Fisher E, Li Y, Burwinkel B, Kühr V, Hoffmann K, Möhling M. et al . Preliminary evidence of FABP2 A54 T polymorphism associated with reduced risk of type 2 diabetes and obesity in women from a German Cohort.  Horm Res Metab. 2006;  38 341-345
    Article in Thieme ConnectPubMedGoogle Scholar

Correspondence

Dr. D. A. de Luis

Professor Associated of Nutrition

Executive Director of Institute of Endocrinology and Nutrition

Medicine School

Valladolid University

C/Los perales 16

47130 Simancas

Valladolid

Spain

Fax: +34/9833/31 56 6

Email: dadluis@yahoo.es

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