Article

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

Institute of Endocrinology and Nutrition, Medicine School and Unit of Investigation, Hospital Rio Hortega, University of Valladolid, RD056/00013 RETICEF, Valladolid, Spain.
Obesity Surgery (Impact Factor: 3.75). 06/2009; 19(12):1691-6. DOI: 10.1007/s11695-009-9859-x
Source: PubMed

ABSTRACT

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.

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    • "In our study the genotype frequencies of FABP2 Ala54/Thr54, Thr54/Thr54 and Ala54/Ala54 in cases were 73.1%, 18.1% and 8.69%; respectively. We have observed that the frequency of Ala54/Thr54 genotype was 73.1% in essential HTN cases, which is significantly higher compared to that in a Spanish (43.7%) population amongst Pre-surgical Morbid Obesity Patients (De Luis et al., 2009). The frequency of allele A was 45.29% in essential HTN cases, which is lower in comparison to Mexican obese patients (74.4%), while the frequency of allele T was 54.7%, which is significantly higher in comparison to the Mexican (25.6) obese patients (Lopez et al., 2007). "
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    ABSTRACT: Background: Hypertension has a multi-factorial background based on genetic and environmental interactive factors. ACE, FABP2 and GST genes have been suggested to be involved in the development of hypertension. However, the results have been inconsistent. Aim: The present study was carried out to investigate the association of ACE (rs4646994), FABP2 (rs1799883) and GST (GSTM1 null or positive genotype and GSTT1 null or positive genotype) genes polymorphism with essential HTN cases and controls. Subjects and methods: This study includes 138 essential hypertension (HTN) patients and 116 age-, sex- and ethnicity-matched control subjects. GST (GSTM1 null or positive genotype and GSTT1 null or positive genotype) genes polymorphisms were evaluated by multiplex PCR, ACE (rs4646994) gene polymorphisms by PCR and FABP2 (rs1799883) gene polymorphisms by PCR-RFLP method. Results: Significant differences were obtained in the frequencies of ACE DD, II genotype (p = 0.006, 0.003), GSTT1 null, GSTM1 positive genotype (p = 0.048, 0.010) and FABP2 Ala54/Ala54 genotype (p = 0.049) between essential HTN cases and controls. Conclusion: It is concluded that ACE (rs 4646994), FABP2 (rs1799883) and GST (GSTM1 null or positive genotype and GSTT1 null or positive genotype) genes polymorphism are associated with HTN. Further investigation with a larger sample size may be required to validate this study.
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    ABSTRACT: The results from the published studies on the association of fatty acid-binding protein 2 (FABP2) Ala54Thr polymorphism with dyslipidemia are conflicting and inconclusive. In this meta-analysis encompassing all the relevant studies, we aimed to investigate the association of the FABP2 Ala54Thr polymorphism with fasting blood lipids. We limited our analysis to the following four blood lipid parameters: total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Subjects were confined to adults who were at least 18 years old. A dominant model was used for this meta-analysis. 30 studies with 14,401 subjects were included in this meta-analysis. The results showed that the carriers of Thr54 allele have higher blood TC and LDL-C than the non-carriers: standardized mean difference (SMD)=0.07, 95% CI (confidence interval, 0.02, 0.11), P=0.005, Pheterogeneity=0.12, and SMD=0.09, 95% CI (0.03, 0.15), P=0.002, Pheterogeneity=0.0006, respectively. Significant association between the Ala54Thr polymorphism and lower blood HDL-C was also detected under the dominant models: SMD=-0.05, 95% CI (-0.09, -0.00), P=0.04, Pheterogeneity=0.10. Our meta-analysis supports the strong association between the Thr54 allele of the FABP2 Ala54Thr polymorphism with higher levels of TC and LDL-C, and lower levels of HDL-C.
    No preview · Article · Jun 2010 · Atherosclerosis
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    ABSTRACT: The results from the published studies on the association of fatty acid-binding protein 2 (FABP2) Ala54Thr polymorphism with insulin resistance and blood glucose are conflicting. In this meta-analysis, we investigated the association of the FABP2 Ala54Thr polymorphism with insulin resistance and blood glucose. We collected data on fasting blood glucose and fasting insulin, 2-h blood glucose (2-h BG) and 2-h insulin (2-h insulin), and homeostasis model assessment insulin resistance index. A dominant model was used for this meta-analysis. Thirty-one studies with 13 451 subjects were included in this meta-analysis. The carriers of Thr54 allele have significantly higher homeostasis model assessment insulin resistance index and marginally higher fasting insulin than the non-carriers: standardized mean difference (SMD) = 0.07, 95% confidence interval (CI, 0.02, 0.12), p = 0.007, p(heterogeneity) = 0.19 and SMD = 0.08, 95% CI (-0.01, 0.17), p = 0.07, p(heterogeneity) < 0.00001, respectively. A borderline significant association between the FABP2 Ala54Thr polymorphism and an increased 2-h BG was also detected under the dominant model: SMD = 0.10, 95% CI (0.00, 0.20), p = 0.05, p(heterogeneity) = 0.09. In addition, a borderline association between this polymorphism and an increased fasting blood glucose in populations of other ethnic origins was detected under the dominant model: SMD = 0.11, 95% CI (-0.00, 0.23), p = 0.06, p(heterogeneity) = 0.03. Our meta-analysis suggests that the Thr54 allele of the FABP2 Ala54Thr is weakly associated with a higher degree of insulin resistance, higher level of fasting insulin and higher level of 2-h BG. Our meta-analysis also suggests a weak association between this polymorphism and an increased fasting blood glucose in populations of other ethnic origins under the dominant model.
    Full-text · Article · Jul 2010 · Diabetes/Metabolism Research and Reviews
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