Search

Background: A transition G to A at codon 54 of FABP2 results in an amino acid substitution (ala 54 to Thr 54). This polymorphism could be associated with insulin resistance and adipocytokines in patients with diabetes mellitus type 2. Objective: The aim of our study was to investigate the influence of Thr54 polymorphism in the FABP2 gene on adipocytokines and insulin resistance in the fasted state in naïve patients with diabetes mellitus type 2. Design: A population of 58 naïve patients with diabetes mellitus type 2 (fasting glucose >126 mg/dl) and obesity (body mass index >30) was analyzed in a prospective way. An indirect calorimetry, tetrapolar electrical bioimpedance, blood pressure, a serial assessment of nutritional intake with 3 days written food records and biochemical analysis (lipid profile, adipocytokines, insulin, CRP and HOMA) 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 second group. Results: Thirty-three patients (56.9%) had genotype Ala54/Ala54 (wild type group) and 25 (43.1%) patients Ala54/Thr54 (19 patients, 32.8%) or Thr54/Thr54 (6 patients, 10.3%) (mutant group). C-reactive protein (5.6±4.2 vs 8.7±5.3 mg/dl: p<0.05), insulin (22.9±11 vs 6.6±12 mUI/L: p<0.05) and HOMA (7.65±5.3 vs 9.1±6.3: p<0.05) were higher in mutant group than wild group. Anthropometric parameters, dietary intakes and adipocytokines were similar in both genotypes. Conclusion: The novel finding of this study is the association of the Thr54/Ala54 and Thr54/ Thr54 FABP2 genotypes with higher levels of C reactive protein, insulin and HOMA. [ABSTRACT FROM AUTHOR]

Background: The alanine to threonine substitution at codon 54 in the FABP2 gene and PPARα Val162 allele have been associated with hypertriglyceridemia. Objective: We sought to determine the prevalence of the Ala54Thr polymorphism of fatty acid binding protein (FABP) 2 gene and the Leu162/Val in exon 5 and G/C in intron7 polymorphism of peroxisome proliferator-activated receptor alpha (PPARα) gene in hypertriglyceridemic patients and their associations with blood lipid concentrations. Methods: A total of 170 hypertriglyceridemic subjects were enrolled and genotyped for Ala54Thr, Leu162Val, and intron 7 polymorphism by the use of a polymerase chain reaction-restriction fragment length polymorphism method. Fasting blood triglyceride, total cholesterol (TC), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein (Apo)B, and ApoCIII also were determined. Results: We found frequency of 81.2% for the Thr54 polymorphism among hypertriglyceridemic subjects. Positive associations were observed between this polymorphism and greater blood triglyceride, very low-density lipoprotein, and ApoCIII levels and lower blood high-density lipoprotein cholesterol concentration both in men and women. However, no association was found between the Thr54 polymorphism and TC, low-density lipoprotein cholesterol, ApoB, and body mass index. Frequency of the Leu162Val polymorphism was 21.8%. The Leu162Val polymorphism was not associated with lipid and lipoprotein concentrations in hypertriglyceridemic subjects (both in men and women). The frequency of intron7 polymorphism was 55.3% in subjects studied and, except for body mass index and TC, no association was found between the intron7 allele and blood lipids ApoB, and ApoCIII. Conclusion: Frequency of the Thr54 polymorphism is high in hypertriglyceridemic subjects, and the presence of this allele may increase some blood lipid and lipoprotein concentrations. In addition, the frequency of intron7 polymorphism may be greater than Leu162Val in hypertriglyceridemic patients. [Copyright &y& Elsevier]

Abstract: Variants of the human intestinal fatty acid binding protein 2 gene (FABP2) are associated with traits of the metabolic syndrome. Relevant FABP2 promoter polymorphisms c.-80_-79insT, c.-136_-132delAGTAG, c.-168_-166delAAGinsT, c.-260G>A, c.-471G>A, and c.-778G>T result in two haplotypes A and B. Activation of haplotypes by rosiglitazone stimulated PPARγ/RXRα leads to 2-fold higher activity of haplotype B than A. As shown by chimeric FABP2 promoter constructs, the higher responsiveness of FABP2 haplotype B is mainly but not solely determined by polymorphism c.-471G>A. As shown by EMSA and promoter–reporter assays, Oct-1 interacts with the −471 region of FABP2 promoters, induces the activities of both FABP2 promoter haplotypes and abolishes the different activities of haplotypes induced by rosiglitazone activated PPARγ/RXRα. In conclusion, our findings suggest a functional role of PPARγ/RXRα and Oct-1 in the regulation of the FABP2 gene. [Copyright &y& Elsevier]

Recent studies underlie the importance of intestinal permeability and chronic inflammation in the pathogenesis of T2DM. Our study compared the concentrations of FABP2 and YKL40 as markers of intestinal permeability and inflammation among normoglycemia, prediabetes and T2DM. We recruited 122 participants (45 normoglycemic, 26 prediabetes, and 51 T2DM) of whom we measured the fasting serum levels of FABP2 and YKL-40 using ELISA method. The levels of FABP2 were significantly higher in the T2DM group [2.890 (1.880–4.070)] in comparison to both prediabetes [2.025 (1.145–2.343), p = 0.0085] and normoglycemia group [1.72 (1.250–2.645), p = 0.011]. The levels of YKL-40 were also significantly higher in the T2DM group [68.70 (44.61–166.6)] in comparison to both prediabetes [28.85 (20.64–41.53), p < 0.0001] and normoglycemia group [28.64 (19.25–43.87), p < 0.001]. Our study observed that the levels of FABP2 and YKL-40 were highest in the T2DM group supporting the available evidences on the role of intestinal permeability disruption and chronic low-grade inflammation in the pathogenesis of T2DM. • Increased gut permeability and Inflammation contribute to the development of Diabetes Mellitus (DM). • Intestinal-Fatty Acid Binding Proteins (FABP2) indicates intestinal permeability. • Chitinase-3-Like Protein 1 (YKL-40) indicates inflammation. • The serum concentration of FABP2 and YKL-40 were higher in diabetes mellitus participants. • The elevated FABP2 and YKL-40 serum proved an increased intestinal permeability and inflammation in DM participants. [ABSTRACT FROM AUTHOR]