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
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
3
Kumada M, Kihara S, Sumitsuji S.
Association of hypoadiponectinemia with coronary artery disease in men.
Arterioscler Thromb Vasc Biol.
2003;
23
85-89
4
Shimomoura I, Hammer RE, Ikemoto S.
Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy.
Nature.
1999;
401
73-76
5
Steppan CM, Bailey ST, Bhat S.
The hormone resistin links obesity to diabetes.
Nature.
2001;
409
307-312
6
Matsuzawa Y.
Adipocytokines: Emerging therapeutic targets.
Curr Atheroscler Rep.
2005;
7
58-62
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
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
9
Besnard P.
Cellular and molecular aspects of fat metabolism in the small intestine.
Proc Nutr Soc.
1996;
5
19-37
10
Nieuwenhoven FA Van, Vusse GJ Van der, Glatz JFC.
Membrane associated and cytoplasmatic fatty acid binding proteins.
Lipids.
1996;
30
S223-S227
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
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
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
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
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
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
17
Suominen P.
Evaluation of an enzyme immunometric assay to measure serum adiponectin concentrations.
Clin Chem.
2004;
50
219-221
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
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
20
Feurer ID, Mullen JL.
Bedside measurement of resting energy expenditure and respiratory quotient via indirect
calorimetry.
Nutr Clin Pract.
1986;
1
43-49
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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