Influence of ALA54THR polymorphism of fatty acid binding protein 2 on lifestyle modification response in obese subjects.
OBJECTIVE
It has been found that the expression of fatty acid binding protein 2 (FABP2) mRNA is under dietary control. A G-to-A transition at codon 54 of FABP2 results in an amino acid substitution (from Ala 54 to Thr 54). This polymorphism was associated with high insulin resistance and high fasting insulin concentrations. The aim of our study was to investigate the influence of Thr54 polymorphism in the FABP2 protein on the response to a lifestyle modification (Mediterranean hypocaloric diet and exercise) in obese patients.


METHODS
A population of 69 obese (body mass index > 30) nondiabetic outpatients was analyzed in a prospective way. Before and after 3 months of the lifestyle modification program, indirect calorimetry, tetrapolar electrical bioimpedance measurement, blood pressure recording, serial assessment of the nutritional intake (3 days of written food records), and biochemical analysis were performed. The lifestyle modification program consisted of a hypocaloric diet (1,520 kcal; 52% carbohydrates, 25% lipids, and 23% proteins). The exercise program consisted of aerobic exercise for at least three times/week (60 min each). Statistical analysis was performed for combined Ala54/Thr54 and Thr54/Thr54 as a mutant group and wild-type Ala54/Ala54 as second group.


RESULTS
The mean age was 45.5 +/- 16.7 years, the mean body mass index was 34.1 +/- 5.1, and there were 14 males (20.3%) and 55 females (79.7%) with a weight loss of 3.17 +/- 3.5 kg (3.5%). Thirty-seven patients (53.6%) had the genotype Ala54/Ala54 (wild-type group) and 32 (46.4%) patients either the genotype Ala54/Thr54 (26 patients, 30.2%) or the genotype Thr54/Thr54 (6 patients, 16.2%). The percentage of responders (weight loss) was similar in both groups (89.2 vs. 90.6%). In the wild-type group, body mass index, weight, fat mass, low-density lipoprotein cholesterol level, and waist circumference decreased, whereas the VO2 (oxygen consumption) increased. In the mutant group, glucose, body mass index, weight, waist circumference, and systolic blood pressure decreased, and VO2 increased. No differences were detected between basal values in both groups. Only the leptin levels showed a significant decrease in the wild-type group (23.85%; p < 0.05), with no statistically significant difference in the mutant group (2.59%; NS). Resistin, tumor necrosis factor alpha, interleukin 6, insulin, and C-reactive protein remained without changes in both groups.


CONCLUSIONS
Weight loss is associated with different changes, depending on the FABP2 genotype. Carriers of the Thr54 allele have a different response than wild-type obese subjects, with a significant decrease of systolic blood pressure and glucose levels in Thr54 carriers and a significant decrease in fat mass, low-density lipoprotein cholesterol, and leptin in wild-type patients.
de Luis
D A
DA
Institute of Endocrinology and Nutrition, Medical School and Unit of Investigation, Hospital Rio Hortega, University of Valladolid, Valladolid, Spain. dadluis@yahoo.es
Aller
R
R
Izaola
O
O
Sagrado
M Gonzalez
MG
Conde
R
R
D000273:Adipose Tissue / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D008078:Cholesterol, LDL / Q000097:blood; D004038:Diet, Reducing; D015444:Exercise / Q000502:physiology; D050556:Fatty Acid-Binding Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D020738:Leptin / Q000097:blood; D008019:Life Style; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000178:diet therapy / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy; D010101:Oxygen Consumption; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D016896:Treatment Outcome; D015431:Weight Loss / Q000235:genetics* / Q000502:physiology
D001786:Blood Glucose; D008078:Cholesterol, LDL; C493404:FABP2 protein, human; D050556:Fatty Acid-Binding Proteins; D020738:Leptin; D012333:RNA, Messenger