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Background: Delirium Tremens (DT) is known to be a serious complication of alcohol withdrawal syndrome (AWS). Neurotransmitter abnormalities, inflammation, and increased permeability are associated with the pathogenesis of AWS and DT. However, the biomarkers of these conditions are still poorly understood. Methods: In this work, biochemical, hematologic, inflammatory, and gut permeability biomarkers were investigated in the following three groups: healthy controls (n = 75), severe AWS patients with DT (n = 28), and mild/moderate AWS without DT (n = 97). Blood sampling was performed after resolution of the acute condition (on 5 ± 1 day after admission) to collect clinical information from patients and to investigate associations with clinical scales. Biomarker analysis was performed using automated analyzers and ELISA. Inflammatory biomarkers included the erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hsCRP), and platelet-to-lymphocyte ratio (PLR). Results: Among the biochemical biomarkers, only glucose, total cholesterol, and alanine aminotransferase (ALT) changed significantly in the analyzed groups. A multiple regression analysis showed that age and ALT were independent predictors of the CIWA-Ar score. Hematologic biomarker analysis showed an increased white blood cell count, and the elevated size and greater size variability of red blood cells and platelets (MCV, RDWc, and PDWc) in two groups of patients. Gut permeability biomarkers (FABP2, LBP, and zonulin) did not change, but were associated with comorbid pathologies (alcohol liver disease and pancreatitis). The increase in inflammatory biomarkers (ESR and PLR) was more evident in AWS patients with DT. Cluster analysis confirmed the existence of a subgroup of patients with evidence of high inflammation, and such a subgroup was more frequent in DT patients. Conclusions: These findings contribute to the understanding of biomarker variability in AWS patients with and without DT and support the heterogeneity of patients by the level of inflammation. [ABSTRACT FROM AUTHOR]

Aim. To study the contribution of the Ala54Thr genetic polymorphism of the FABP2 gene to the risk of developing type 2 diabetes mellitus among the Yakut population. Materials and methods. The study included participants who filled out a questionnaire approved by the Local Committee on Biomedical Ethics at the Yakut Science Centre of complex medical problems and voluntarily signed an informed consent to conduct a genetic study. The sample consisted of 181 patients of the endocrinological department of the Republican Hospital No. 2 of the State Budgetary Institution “Center for Emergency Medical Care“ with a diagnosis of type 2 diabetes. The comparison group was a sample of 336 volunteers without chronic diseases of the Yakut ethnicity. For molecular genetic analysis, genomic DNA samples were isolated from whole blood. Single nucleotide polymorphism was determined by polymerase chain reaction followed by analysis of restriction fragment length polymorphism. Results. Study showed that polymorphism in the FABP2 gene has an impact on anthropometric parameters and blood biochemical parameters. The risk of developing type 2 diabetes was 1.7 times higher in carriers of the Ala/Thr genotype (odds ratio 1.755, 95% confidence interval – 1.212–2.542; p0.005) compared with carriers of other genotypes. When comparing the average biochemical values, the levels of aspartate transaminase, alanine aminotransferase, glucose and total bilirubin in homozygous carriers of the Ala/Ala genotype were significantly lower than in carriers of other genotypes (р0.05). Carriers of the heterozygous Ala/Thr genotype (р0.05) had the highest level in terms of aspartate aminotransferase and alanine aminotransferase. The highest indicator of the average level of HbA1c and an indicator of total bilirubin were carriers of the Thr/Thr genotype (р0.05). Conclusion. The high prevalence of the negative Thr allele among the Yakut population is probably associated with living conditions in the North, as well as in the traditional type of diet.

Background: Recently, the hypothesis that pathological α-Synuclein propagates from the gut to the brain has gained attention. Although results from animal studies support this hypothesis, the specific mechanism remains unclear. This study focused on the intestinal fatty acid-binding protein (FABP2), which is one of the subtypes of fatty acid binding proteins localizing in the gut, with the hypothesis that FABP2 is involved in the gut-to-brain propagation of α-Synuclein. The aim of this study was to clarify the pathological significance of FABP2 in the pathogenesis and progression of synucleinopathy. Methods: We examined the relationship between FABP2 and a-Synuclein in the uptake of α-Synuclein into enteric neurons using primary cultured neurons derived from mouse small intestinal myenteric plexus. We also quantified disease-related protein concentrations in the plasma of patients with synucleinopathy and related diseases, and analyzed the relationship between plasma FABP2 level and progression of the disease. Results: Experiments on α-Synuclein uptake in primary cultured enteric neurons showed that following uptake, α-Synuclein was concentrated in areas where FABP2 was localized. Moreover, analysis of the plasma protein levels of patients with Parkinson's disease revealed that the plasma FABP2 and α-Synuclein levels fluctuate with disease duration. The FABP2/α-Synuclein ratio fluctuated more markedly than either FABP2 or α-Synuclein alone, depending on the duration of disease, indicating a higher discriminant ability of early Parkinson's disease patients from healthy patients. Conclusions: These results suggest that FABP2 potentially contributes to the pathogenesis and progression of α-Synucleinopathies. Thus, FABP2 is an important molecule that has the potential to elucidate the consistent mechanisms that lead from the prodromal phase to the onset and subsequent progression of synucleinopathies. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) still lacks valuable diagnostic and prognostic tools. This study aimed to investigate the potential diagnostic and prognostic value of baseline interleukin (IL)-10, fatty acid-binding protein 2 (FABP2) and lipopolysaccharide (LPS) levels in patients with HCC. Serum levels of IL-10, FABP2 and LPS in 47 newly diagnosed HCC patients and 50 healthy individuals were estimated and compared. The best cut-off points for baseline IL-10, FABP2 and LPS levels predicting overall survival (OS) were evaluated. Both levels of FABP2 and IL-10 were significantly higher in HCC patients vs. control group (median 2095 vs. 1772 pg/mL, p = 0.026; 9.94 vs. 4.89 pg/mL, p < 0.001) and may serve as potential biomarkers in complex HCC diagnostic tools. The cut-off value of 2479 pg/mL for FABP2 was determined to have the highest sensitivity (66.7%) and specificity (55.6%) to distinguish patients with a median OS longer than 17 months. However, the median OS of patients with high and low levels of FABP2 were not significantly different (p = 0.896). The prognostic value of LPS as well as FABP2 and IL-10 for HCC patients appears to be limited. [ABSTRACT FROM AUTHOR]

Introduction: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders mainly representing impaired social communication. The etiology of ASD includes genetic and environmental risk factors. Rodent models containing ASD risk gene mutations or environmental risk factors, such as exposure to maternal inflammation, show abnormal behavior. Although zebrafish conserves many important brain structures of humans and has sophisticated and fine behaviors in social interaction, it is unknown whether the social behaviors of their offspring would be impaired due to exposure to maternal inflammation. Methods: We exposed zebrafish to maternal immune activation (MIA) by injection with polyinosinic:polycytidylic acid [poly(I:C)], and screened their behaviors through social behavioral tests such as social preference and shoaling behavior tests. We compared phenotypes resulted from different ways of poly(I:C) exposure. RNA sequencing was performed to explore the differential expression genes (DEGs). Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) network analysis was performed with the detected DEGs to find the concentrated pathways. Finally, we knocked out the fatty acid-binding protein 2 (fabp2), a key node of the concentrated PPI network, to find its rescues on the altered social behavior. Results: We reported here that MIA offspring born to mothers injected with poly(I:C) exhibited impaired social approach and social cohesion that mimicked human ASD phenotypes. Both maternal exposure and direct embryo exposure to poly(I:C) resulted in activations of the innate immune system through toll-like receptors 3 and 4. RNA-sequencing results from MIA brain tissues illustrated that the numbers of overexpressed genes were significantly more than that of underexpressed genes. GO and KEGG analyses found that MIA-induced DEGs were mainly concentrated in complement and coagulation cascade pathways. PPI network analyses suggested that villin-1 (vil1) pathway might play a key role in MIA-induced ASD. Knockout of fabp2 in F0 zebrafish rescued the social behavior deficits in MIA offspring. Conclusions: Overall, our work established an ASD model with assessable behavior phenotype in zebrafish and provided key insights into environmental risk factor in ASD etiology and the influence of fabp2 gene on ASD-like behavior. [ABSTRACT FROM AUTHOR]

IntroductionAutism spectrum disorder (ASD) is a group of neurodevelopmental disorders mainly representing impaired social communication. The etiology of ASD includes genetic and environmental risk factors. Rodent models containing ASD risk gene mutations or environmental risk factors, such as exposure to maternal inflammation, show abnormal behavior. Although zebrafish conserves many important brain structures of humans and has sophisticated and fine behaviors in social interaction, it is unknown whether the social behaviors of their offspring would be impaired due to exposure to maternal inflammation.MethodsWe exposed zebrafish to maternal immune activation (MIA) by injection with polyinosinic:polycytidylic acid [poly(I:C)], and screened their behaviors through social behavioral tests such as social preference and shoaling behavior tests. We compared phenotypes resulted from different ways of poly(I:C) exposure. RNA sequencing was performed to explore the differential expression genes (DEGs). Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein–protein interaction (PPI) network analysis was performed with the detected DEGs to find the concentrated pathways. Finally, we knocked out the fatty acid-binding protein 2 (fabp2), a key node of the concentrated PPI network, to find its rescues on the altered social behavior.ResultsWe reported here that MIA offspring born to mothers injected with poly(I:C) exhibited impaired social approach and social cohesion that mimicked human ASD phenotypes. Both maternal exposure and direct embryo exposure to poly(I:C) resulted in activations of the innate immune system through toll-like receptors 3 and 4. RNA-sequencing results from MIA brain tissues illustrated that the numbers of overexpressed genes were significantly more than that of underexpressed genes. GO and KEGG analyses found that MIA-induced DEGs were mainly concentrated in complement and coagulation cascade pathways. PPI network analyses suggested that villin-1 (vil1) pathway might play a key role in MIA-induced ASD. Knockout of fabp2 in F0 zebrafish rescued the social behavior deficits in MIA offspring.ConclusionsOverall, our work established an ASD model with assessable behavior phenotype in zebrafish and provided key insights into environmental risk factor in ASD etiology and the influence of fabp2 gene on ASD-like behavior.

Hepatocellular carcinoma (HCC) still lacks valuable diagnostic and prognostic tools. This study aimed to investigate the potential diagnostic and prognostic value of baseline interleukin (IL)-10, fatty acid-binding protein 2 (FABP2) and lipopolysaccharide (LPS) levels in patients with HCC. Serum levels of IL-10, FABP2 and LPS in 47 newly diagnosed HCC patients and 50 healthy individuals were estimated and compared. The best cut-off points for baseline IL-10, FABP2 and LPS levels predicting overall survival (OS) were evaluated. Both levels of FABP2 and IL-10 were significantly higher in HCC patients vs. control group (median 2095 vs. 1772 pg/mL, p = 0.026; 9.94 vs. 4.89 pg/mL, p < 0.001) and may serve as potential biomarkers in complex HCC diagnostic tools. The cut-off value of 2479 pg/mL for FABP2 was determined to have the highest sensitivity (66.7%) and specificity (55.6%) to distinguish patients with a median OS longer than 17 months. However, the median OS of patients with high and low levels of FABP2 were not significantly different (p = 0.896). The prognostic value of LPS as well as FABP2 and IL-10 for HCC patients appears to be limited.

Context Dyslipidemia is a multifactorial disease in which lipoproteins play an important role as one of the early markers for coronary heart disease (CHD). Mixed dyslipidemia is common in people with diabetes mellitus, but nondiabetic dyslipidemics (NDD) remain unidentified for the risk of developing dyslipidemia and eventually CHD. Objectives This pilot study attempts to analyze the genetic basis of lipid metabolism alterations, emphasizing the association between fatty acid-binding protein-2 (FABP2-Ala54Thr) and apolipoprotein-C3 (APOC3-rs5128) genetic polymorphism, as a risk for developing dyslipidemia and CHD in NDD. Methods and Design Total 90 subjects—30 DD, 30 NDD, and 30 apparently healthy subjects representing Central India—were included. Biochemical analysis and DNA genotyping were done by polymerase chain reaction restriction fragment length polymorphism. Statistical Analysis The biochemical parameters were reported as means ± standard deviation. One-way analysis of variance test was used to compare biochemical parameters of three groups. Chi-squared test was done to compare genotype distributions. The strength of association was assessed by odds ratios (ORs) with 95% confidence intervals (CIs). All statistical analysis was done using SPSS-PC software and Graph Pad. Results In NDD, maximum polymorphism was observed followed by DD and least polymorphism was observed in controls. There was a significant association of APOC3 G allele with occurrence of hypertriglyceridemia (p < 0.05); however, no such association was found for FABP2 A allele (p > 0.05). Logistic regression analysis revealed APOC3 polymorphism to be significantly associated with dyslipidemia (OR = 2.6667, 95% CI = 1.0510–6.7663, p = 0.0341); no such association was found for FABP2 polymorphism (OR = 0.4643, 95% CI = 0.1641–1.3136, p = 0.1347). The triglyceride and cholesterol values in individuals with homozygous genotype indicate that genetic study is comparable to the biochemical findings in carriers of polymorphic allele than noncarriers, especially in NDD patients. Conclusions Pilot study indicates that the presence of APOC3 gene polymorphism is associated with pro-atherogenic dyslipidemia in nondiabetic patients and may raise risk of CHD. This information could be used for preventive strategies in NDD group that may otherwise go unnoticed. [ABSTRACT FROM AUTHOR]

Aim.To study the possibility of using polymorphisms of genesTCF7L2,FABP2,KCNQ1,ADIPOQas markers for predicting the development of type 2 diabetes mellitus (T2D) in the population of Novosibirsk. Materials and methods.On the basis of prospective observation of a representative population sample of residents of Novosibirsk (HAPIEE), 2 groups were formed according to the case-control principle (case people who had diabetes mellitus 2 over 10 years of observation, and control people who did not developed disorders of carbohydrate metabolism). T2D group (n=443, mean age 56.26.7 years, men 29.6%, women 70.4%), control group (n=532, mean age 56.17.1 years, men 32.7%, women 67.3%). DNA was isolated by phenol-chloroform extraction. Genotyping was performed by the method of polymerase chain reaction with subsequent analysis of restriction fragment length polymorphism, polymerase chain reaction in real time. Statistical processing was carried out using the SPSS 16.0 software package. Results and discussion.No significant effect of rs1799883 of theFABP2gene, rs2237892 of theKCNQ1gene, and rs6773957 of theADIPOQgene on the risk of developing T2D was found. Genotypes TT and TC rs7903146 of theTCF7L2gene are genotypes for the risk of developing T2D (relative risk RR 3.90, 95% confidence interval CI 2.316.61,p0.001; RR 1.86, 95% CI 1.422.43,p0.001, respectively). The CC genotype rs7903146 of theTCF7L2gene is associated with a protective effect against T2D (RR 0.37, 95% CI 0.290.49,p0.001). When theTCF7L2gene is included in the model for assessing the risk of developing T2D rs7903146, it retains its significance in both men and women. Conclusion.The rs7903146 polymorphism of theTCF7L2gene confirmed its association with the prognosis of the development of T2D, which indicates the possibility of considering it as a candidate for inclusion in a diabetes risk meter. Variants of risk meters have been developed to assess the prognosis of the development of diabetes mellitus 2 in men and women aged 4569 years during 10 years of follow-up. The association with the prognosis of the development of T2D polymorphisms rs1799883 of theFABP2gene, rs2237892 of theKCNQ1gene and rs6773957 of theADIPOQgene was not found.

S100A4 is primarily expressed in intestinal macrophages, and promotes colonic inflammation and colitis-associated colon tumorigenesis. Smad4 is also expressed in the colon; however, it inhibits colitis-associated cancer (CAC) development. The specific role of Smad4 in S100A4 + cells in CAC remains unknown. In this study, an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced CAC model was established in mice with S100A4 + cell-specific Smad4 deletion (S100A4 Smad4-/- ). Smad4 deficiency in S100A4 + cells exacerbated DSS-induced colitis and promoted colorectal tumorigenesis. In addition, S100A4 + cell-specific Smad4 ablation promoted the M2 polarization of macrophages in CAC. Mechanistically, Smad4 depletion in macrophages enhanced lipid metabolism by activating the FA binding protein 2 (Fabp2)/STAT6 pathway. Furthermore, Smad4 deficiency in macrophages promoted MC38 tumor growth in myeloid-specific Smad4 deficient (Lyz Smad4-/- ) mice, whereas blocking Fabp2 expression reversed the tumor growth. Additionally, high Smad4 expression was associated with prolonged survival in patients with colorectal cancer. Thus, Smad4 in S100A4 + macrophages plays a tumor-inhibiting role in CAC development and supports its use as a prognostic marker in CRC patients., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Type 2 diabetes mellitus, a rapidly growing epidemic, and its frequently related complications demand global attention. The two factors commonly attributed to the epidemic are genetic factors and environmental factors. Studies indicate that the genetic makeup at an individual level and the environmental aspects influence the occurrence of the disease. However, there is insufficiency in understanding the mechanisms through which the gene mutations and environmental components individually lead to T2DM. Also, discrepancies have often been noted in the association of gene variants and type 2 diabetes when the gene factor is examined as a sole attribute to the disease. Study: In this review initially, we have focused on the proposed ways through which CAPN10, FABP2, GLUT2, TCF7L2, and ENPP1 variants lead to T2DM along with the inconsistencies observed in the gene-disease association. The article also emphasizes on obesity, lipoprotein profile, and nutrition as environmental factors and how they lead to T2DM. Finally, the main objective is explored, the environment-gene-disease association i.e. the influence of each environmental factor on the aforementioned specific gene-T2DM relationship to understand if the disease-causing capability of the gene variants is exacerbated by environmental influences. Conclusion: We found that environmental factors may influence the gene-disease relationship. Reciprocally, the genetic factors may alter the environment-disease relationship. To precisely conclude that the two factors act synergistically to lead to T2DM, more attention has to be paid to the combined influence of the genetic variants and environmental factors on T2DM occurrence instead of studying the influence of the factors separately. [ABSTRACT FROM AUTHOR]

Copyright of Acibadem Saglik Bilimleri Dergisi is the property of Acibadem University Medical School and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Intestinal fatty-acid binding protein (I-FABP, also called FABP2) is involved in the uptake of dietary fatty acids in the intestine, and its binding specificity is only with long-chain fatty acid. In this study, sequences of 4 exons in pigeon FABP2 were successfully amplified. The encoded protein had a molecular weight of 15.13 kDa and the theoretical pI was 6.75. Bioinformatics analysis indicated that the protein was predicted to contain 10 potential phosphorylation sites and did not contain signal peptide structure. The evolutionary analysis suggested the amino acid sequence of pigeon FABP2 was closest to the mallard (Nippoia nippon) homologs. Meanwhile the expression of FABP2 mRNA in different ages and tissues we conducted. It showed that the expression of the FABP2 gene was the highest in the liver, followed by the small intestine and adipose tissue, while lowest in the breast muscle. Also, the expression level in the gizzard was gradually increased with aging. Our results may serve as reference to better studies of the functional characterization and structure of the FABP2 in pigeon.

Currently there is no reliable tool available to monitor gastrointestinal function in the critically ill. Biomarkers are therefore of great interest in this field as the lack of monitoring tools impedes any interventional studies. The potential biomarkers citrulline and intestinal fatty acid-binding protein (I-FABP) are the present focus. Targeted literature searches were undertaken for physiology and pathophysiology, sampling, measurement methods and clinical use of citrulline and I-FABP as biomarkers of intestinal function and injury. Physiology and pathophysiology, specific aspects of sampling and different laboratory assays are summarized and respective pitfalls outlined. Studies in animals and patients outside the ICU support the rationale for these biomarkers. At the same time, evidence in critically ill patients is not yet convincing, several specific aspects need to be clarified, and methodology and interpretation to be refined. We conclude that there are good physiological rationales for citrulline as a marker of enterocyte function and for I-FABP as a marker of intestinal injury, but further studies are needed to clarify whether and how they could be used in daily practice in caring for critically ill patients.

Copyright of Gaceta Médica de Caracas is the property of Academia Nacional de Medicina and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Fatty acid-binding protein 2 (Fabp2), which is involved in the transport of long-chain fatty acids, is widely studied in mammals. Nevertheless, the role of this protein in teleost fish is mostly unknown. Here, we produced a fabp2−/− zebrafish (KO) animal model. Compared with wild-type zebrafish (WT), KO had a markedly decreased content of intestinal n-3 poly-unsaturated fatty acids (n-3 PUFAs) and increased levels of intestinal, hepatic, and serum triacylglycerols (TAG). The intestinal transcriptome analysis of KO and WT revealed an obviously disrupted TAG metabolism and up-regulated bile secretion in KO. Expression levels of the genes related to fatty acid transport and cholesterol (CL) absorption in the intestine of KO were significantly lower than those of WT, while the expression levels of genes related to intestinal TAG synthesis and hepatic CL synthesis were in the opposite direction. To confirm these findings, we further established fabp2 transgenic zebrafish (TG). Compared with WT, TG had a markedly increased content of intestinal n-3 PUFAs, a significantly decreased level of hepatic TAG, and significantly higher expression of genes related to fatty acid transport and CL absorption in the intestine. In conclusion, this study suggests that teleost fish fabp2 could promote intestinal n-3 PUFA absorption to mediate TAG synthesis and CL homeostasis, by regulating the genes involved in lipid metabolism. [ABSTRACT FROM AUTHOR]

Abstract Fatty acid-binding protein 2 (FABP2) is involved in the uptake of dietary fatty acids and intracellular fatty acid transport. In the present study, cDNA of fabp2 in loach (Misgurnus anguillicaudatus) was cloned and its full length was 956 bp, encoding 134 amino acids. Gene expression of fabp2 was investigated in different development stages and different tissues of loach, showing that the expression of fabp2 was recorded at 2 days after hatching (DAH), 10DAH, 20DAH and 35DAH, and higher in loach intestine, muscle and brain, compared with other tissues. We also investigated the effects of dietary oxidized fish oil (OFO) on the expression of intestinal fabp2 in loach juveniles by using fluorescence in situ hybridization (FISH) and real-time quantitative PCR. Fabp2 gene was expressed mainly by the intestinal epithelium cells of loach juveniles. The expression of intestinal fabp2 in loaches fed with OFO diet was significantly up-regulated on day 1 and 3, and down-regulated on day 10 after feeding, compared with those loaches fed with dietary fresh fish oil (FO), which were in accordance with the fluorescence intensities of FISH exhibiting in the corresponding feeding time. The present study indicated that dietary oxidized fish oil could affect the expression of fabp2 in the loach. Our results serve as reference to better understand the functional characterization of fabp2 in loach and other fish species. Graphical abstract Unlabelled Image Highlights • Fabp2 was cloned and characterized in loach. • Spatiotemporal expressions of fabp2 were investigated. • Dietary oxidized fish oil could affect the expression of intestinal fabp2 in the loach. [ABSTRACT FROM AUTHOR]

• The FABP2 rs10857064 was significantly associated with increased obesity risk only in the women under the additive model. • The presence of the rs10857064-G allele were not significantly associated with obesity in other with genetic models (recessive, dominant, over-dominant, and genotypic) in Iranian population. • The TG haplotype containing rs7670862 and rs10857064 could significantly enhance the risk of obesity in only women, not in men. FABP2 is one of the key genes involved in obesity development across different populations. However, there is no comprehensive report about the FABP2 contribution to obesity incidence among Iranians. Hence, the present study was designed to assess the probable role of FABP2 polymorphisms in obesity incidence in the Tehran Cardio- metabolic Genetic Study (TCGS) representative Iran population. Unrelated adults who had BMI information for at least 3 consecutive phases of the TCGS cohort were included. The control and case groups were defined as individuals who always had long-term persistent normal weight (20 < BMI < 25; n = 1526) and individuals who were long-term persistent obese (30 < BMI < 35; n = 1313), respectively. The logistic regression test was used to assess the possible association between SNPs located in and around the FABP2 gene with obesity. Also, we used Haploview and SHEsis to perform haplotype analysis to detect whether or not this chromosomal region is correlated with obesity. We found a gender-dependent association between the rs10857064 FABP2 and the risk of obesity. The presence of the rs10857064-G allele could significantly increase the risk of obesity only in women, not men (OR = 1.26; 95 % CI: 1.02–1.57; p = 0.03). Through haplotype analysis, we also detected that the TG haplotype containing rs7670862 and rs10857064 could significantly enhance the risk of obesity in women, further supporting the central role of rs10857064 in women's long-term obesity risk. In the current study, we revealed that rs10857064-G FABP2 can significantly predispose women to develop obesity. It highlights the importance of different genetic variants in both genders, which could help us to distinguish more efficient obesity screening tests and treatments based on gender in the future. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy is a major cause of morbidity and mortality in type 1 diabetes mellitus (T1DM). Fatty acid binding proteins (FABP1 and FABP2) play a role in the development and progression of chronic kidney disease including type 2 diabetes mellitus. We assessed serum FABP1 and FABP2 levels in children and adolescents with T1DM as potential markers for diabetic nephropathy and their relation to carotid intima media thickness (CIMT). Sixty patients with T1DM were divided into 2 groups according to the presence of nephropathy and compared with 30 healthy controls. CIMT, fasting blood glucose (FBG), hemoglobin A1c (HbA1c), urinary albumin creatinine ratio (UACR), fasting lipid profile and serum FABP1 and FABP2 levels were assessed. FABP1 and FABP2 levels were significantly higher among type 1 diabetic patient with and without nephropathy compared with healthy controls with the highest levels among patients with nephropathy (p < 0.001). There were significant positive correlations between FABP1 and FABP2 and each of systolic blood pressure, CIMT, FBG, HbA1c and total cholesterol among T1DM patients. FABP1 was negatively correlated to glomerular filtration rate. Multivariable linear regression analysis showed that systolic blood pressure, CIMT, FBG and HbA1c were the significant independent variables related to FABP1 levels in type 1 diabetic patients with nephropathy. ROC curve analysis was performed to determine the cutoff value of FABP1 and FABP2 that could detect nephropathy. FABP1 and FABP2 levels are elevated in children and adolescents with T1DM and could represent a link between diabetic nephropathy and subclinical atherosclerosis. • We assessed serum FABP1 and FABP2 levels in children and adolescents with T1DM. • Elevated FABP1 and FABP2 levels were associated with microalbuminuria in pediatric patients with T1DM. • FABP1 and FABP2 were positively correlated to CIMT. • FABP1 and FABP2 represent a link between diabetic nephropathy and subclinical atherosclerosis. [ABSTRACT FROM AUTHOR]

Here we describe the evolutionary relationship of the duplicated intestinal fatty acid binding protein genes fabp2a and fabp2b from medaka and three-spined stickleback by comparing them to the well-studied fabp2 gene from zebrafish. The duplicated fabp2 genes from medaka and three-spined stickleback consist of four exons separated by three introns, which code for a polypeptide of 132 amino acids. Fabp2a and Fabp2b of medaka and three-spined stickleback share highest sequence identity with zebrafish Fabp2. All Fabp2/FABP2 sequences from vertebrates form a distinct clade in a neighbor-joining phylogenetic tree with a robust 100% bootstrap value, which indicates that the medaka and three-spined stickleback fabp2a and fabp2b are orthologs of zebrafish fabp2. The syntenic genes of fabp2a and fabp2b from medaka and three-spined stickleback were shown to be conserved with the syntenic genes of fabp2/ FABP2 from zebrafish and human, evidence that the duplicated fabp2 genes from medaka and three-spined stickleback most likely arose from the teleost-specific whole-genome duplication. The tissue-specific distribution of medaka and three-spined stickleback fabp2a and fabp2b transcripts, and zebrafish fabp2 transcripts, assayed by RT-qPCR suggests the acquisition of new function(s) by the medaka fabp2a, and the distinct evolution of fabp2b compared with fabp2a in the medaka and three-spined stickleback genomes. [ABSTRACT FROM AUTHOR]

Abstract: In the present study full-length cDNAs corresponding to three isoforms of intestinal fatty acid binding protein (fabp2) in Atlantic salmon were cloned and characterized. Gene expression of fabp2 was observed in all tissues investigated, although differences were observed between isoforms. The highest fabp2a1, fabp2a2, and fabp2b expression was in the intestine. A 15kDa protein, corresponding to putative Fabp2 protein, was identified by immunoblotting using anti-human Fabp2 antibody. Immunoblotting and immunohistochemistry confirmed that Fabp2 protein was present in most Atlantic salmon tissues. Similar to gene expression, intestinal tissues had the highest Fabp2 protein levels, decreasing gradually from proximal to distal intestine. During development of distal intestinal inflammation caused by dietary soybean meal from 0 to 21days, Fabp2 decreased significantly on both transcriptional and protein levels. The reduction in Fabp2 was preceded by a down regulation of peroxisome proliferator activated receptor (ppar) alpha and gamma, fabp2''s presumed regulatory proteins, and followed by a progressive increase in proliferating cell nuclear antigen (Pcna) staining. Results illustrate that the early decline of distal intestinal fabp2 was likely caused by a down regulation of their regulatory proteins, but at later time points reduced Fabp2 may largely be due to a less mature enterocyte population resulting from rapid cell turnover. [Copyright &y& Elsevier]

Introduction: Metabolic syndrome (MetS) is a multifactorial disorder in which dyslipidemia plays an important role. Fatty acid-binding protein 2 (FABP 2) is responsible for transport of free fatty acids in the intestinal endothelium cells. FABP2-genetic variants might affect plasma lipid concentrations and intracellular lipid transport. The aim of this study was to investigate the association between FABP2 Ala54Thr genetic polymorphism and metabolic syndrome and some biochemical and anthropological parameters in elderly subjects. Materials and methods:This cross-sectional study included 140 men and 176 women older than 70 years. Fasting serum concentration of glucose, lipid parameters, total proteins and C-reactive protein were determined by standardized methods. Presence (MetS(+)) or absence (MetS(-)) of MetS was determined according to criteria of the International Diabetes Federation. FABP2 genetic polymorphism Ala54Thr (rs1799883) was genotyped with PCR-RFPL. Results: The genotype frequencies for Ala/Ala, Ala/Thr and Thr/Thr genotype were 60, 36 and 6 in MetS(-), and 131, 70 and 13 in MetS(+), respectively, without statistical significance (P = 0.567). Ala/Ala genotype was a subgroup of non-carriers, while Ala/Thr and Thr/Thr genotypes were Thr54-carriers. Median triglyceride concentration was significantly lower in carriers then in non-carriers for whole MetS(+) group (P = 0.050); there were no significant difference between men with MetS (P = 0.144), but there was a difference between women with MetS (P = 0.020). T-test showed that mean HDL cholesterol concentrations in MetS(+) group for Thr54-carriers was significantly higher in whole group (P = 0.001), and for both genders (men P = 0.039; women P = 0.004) as compared to non-carriers. Conclusions: FABP2 genetic polymorphism is associated with lower triglyceride and higher HDL-cholesterol concentrations in elderly subjects with MetS. This genetic variation might be a useful marker for understanding dyslipidemia in MetS. [ABSTRACT FROM AUTHOR]

The fatty-acid-binding protein-2 ( FABP2) gene has been proposed as a candidate gene for diabetes because the encoded protein is involved in fatty acid absorption and therefore may affect insulin sensitivity and glucose metabolism. The rare haplotype (B) of its promoter was shown to be associated with a lower risk for type 2 diabetes. The aim of this study was to investigate whether a polymorphism in the FABP2 promoter does affect the metabolic response to either an medium-chain triacylglycerol (MCT) or an long-chain triacylglycerol (LCT) diet, which were suggested to differ in transport mechanisms, in affinity to FABP2, in activating transcription factors binding to the FABP2 promoter and in their effects on insulin sensitivity. We studied 82 healthy male subjects varying in the FABP2 promoter (42 homozygous for common haplotype (A), 40 homozygous for the rare haplotype (B)) in an interventional study with either an MCT or LCT diet over 2 weeks to examine gene-nutrient interaction. The saturation grade of MCT was adjusted to that of the LCT fat. We determined glucose, insulin, triacylglycerols (TGs), chylomicron triacylglycerols and cholesterol before and after a standardised mixed meal before and after the intervention. HDL cholesterol increased in all groups, which was most pronounced in subjects homozygous for the common promoter haplotype A who received MCT diet ( P = 0.001), but not significant in homozygous rare haplotype B subjects who received MCT fat. Subjects homozygous for FABP2 haplotype A showed a significant decrease in fasting and postprandial glucose ( P = 0.01, 0.04, respectively) and a decrease in insulin resistance (HOMA-IR, P = 0.04) during LCT diet. After correction for multiple testing, those effects did not remain significant. Fasting and postprandial triacylglycerols, LDL cholesterol, chylomicron TGs and cholesterol were not affected by genotype or diet. MCT diet increased HDL cholesterol dependent on the FABP2 promoter haplotype. The effects of the promoter haplotype B could be mediated by PPARγ, which is upregulated by medium-chain fatty acids. [ABSTRACT FROM AUTHOR]

Abstract: Fatty acid-induced damage in pancreatic β-cells is assumed to play an important role in the development of type 2 diabetes. Lactogens (prolactin, placental lactogen and growth hormone) improve β-cell survival via STAT5 activation but the molecular targets are incompletely characterized. The aim of this study was to examine the effect of human growth hormone (hGH) on mRNAs of fatty acid transport and binding proteins expressed in pancreatic β-cells, and to examine this in relation to β-cell survival after exposure to fatty acids. hGH decreased mRNA levels of FAT/CD36, whereas mRNAs of GPR40, FASN, FABP2, FATP1 and FATP4 were unchanged. RNAi against FAT/CD36 decreased fatty acid-induced apoptosis. Over-expression of constitutively active STAT5 was able to mimic hGH’s suppression of FAT/CD36 expression, whereas dominant negative STAT5 was unable to block the effect of hGH indicating that STAT5 did not bind directly to the FAT/CD36 promoter. The hGH-mediated suppression of FAT/CD36 mRNA was associated with a decrease in palmitate uptake and fatty acid-induced basal hyper-secretion of insulin resulting in improved glucose-stimulated insulin secretion. This study suggests that hGH can protect β-cells against fatty acid-induced damages. [Copyright &y& Elsevier]

Background: A transition of guanin to alanin at codon 54 of the fatty acid-binding protein 2 gene (FABP2) results in an amino acid substitution (Ala54 to Thr54). This polymorphism was associated with some cardiovascular risk factors. Objective: The aim of our study was to investigate the influence of the Thr54 polymorphism in the FABP2 gene on obesity anthropometric parameters and cardiovascular risk factors in the fasted state in obese subjects and the allelic distribution of this polymorphism in a geographic area of Spain. Design: A population of 264 obese subjects was analyzed in a cross-sectional study from all health centers of Castilla y Leon (Spain). A nutritional and biochemical evaluation was performed. The statistical analysis was performed for the combined Ala54/Thr54 and Thr54/Thr54 genotype as a dominant model. Results: The mean age was 41.1 ± 13.1 years and the mean BMI 36.5 ± 5.9, with 94 males (35.6%) and 170 females (74.4%). One hundred and fifty-three subjects (58%) had the genotype Ala54/Ala54 (wild-type group) and 111 (42%) participants had the genotype Ala54/Thr54 (n = 92, 34.8%) or Thr54/Thr54 (n = 19, 7.2%) (mutant-type group). The health area of Valladolid had a lower frequency of wild-type genotype and Ala54 allelic frequency than all the other health areas of Castilla y Leon. C-reactive protein was higher in the mutant-type than the wild-type group (3.4 ± 5.6 vs. 7.9 ± 10.4 mg/dl; p < 0.05). Conclusion: The finding of this study is the association of the Thr54/Ala54 and Thr54/Thr54 FABP2 phenotypes with higher levels of C-reactive protein without relation to insulin resistance. Frequencies of this polymorphism are different among health areas of Castilla y Leon. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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]

The article discusses a study which examined the effect of Thr54 polymorphism in the fatty acid binding protein 2 (FABP2) gene on obesity anthropometric parameters, cardiovascular risk and adipocytokines in patients with presurgical morbid obesity. The study assessed the nutritional intake of 55 morbid obese patients for three days. It discovered a link between Thr54 allele and insulin resistance, leptin and adiponectin levels in obese patients.

• The high expression of MSTN and IGF2BP1 inhibited the development of embryonic muscle of white feather Muscovy duck. • FABP2 promotes embryonic muscle development of white feather Muscovy Duck. • The expressions of MSTN, IGF2BP1 and FABP2 mRNA in embryonic white feather Muscovy duck were gender and embryo age specific. To explore the effects of growth-related genes in both sexes and at different growth and development stages, male and female white Muscovy ducks at embryonic day E13, E17, E21, E25 and E29 were assessed in this study. RT-qPCR was used to determine the mRNA transcription levels of selected growth-related genes in the leg muscles of Muscovy ducks of both sexes and at different growth and developmental stages. MSTN , IGF2BP1 and FABP2 mRNAs were expressed in the leg muscles of male and female Muscovy ducks, but with different expression patterns. The MSTN and IGF2BP1 mRNA expression patterns were wavelike. MSTN mRNA expression was elevated at E13, increased at E17, decreased rapidly to the lowest level at E21, increased again at E25, and then decreased. IGF2BP1 mRNA expression was elevated at E13, increased at E17, decreased rapidly at E21, decreased rapidly to the lowest level at E25, and increased at E29. The expression trend of FABP2 mRNA was approximately "⊥" shape; the expression was the lowest at E13, increased slowly from E17 to E25, and increased extremely significantly at E29. In addition, the expression of MSTN in male Muscovy ducks was significantly higher than that in female ducks at E25 (P < 0.05). The expression of IGF2BP1 in male Muscovy ducks was extremely significantly higher than that in female ducks at E17 (P < 0.01). However, the expression of FABP2 in female Muscovy ducks was extremely significantly higher than that in male Muscovy ducks at E21 and E29 (P < 0.01). In conclusion, the mRNA expression of MSTN , IGF2BP1 and FABP2 in white Muscovy ducks is gestational age specific and sex specific. The differential gene expression patterns observed in this study provide a basis for understanding the physiological changes in white Muscovy ducks at different embryonic ages and in both sexes, supplementing the existing research on duck embryo muscle development. In addition, the findings provide a new framework for further discussion of poultry breeding. [ABSTRACT FROM AUTHOR]

Abstract: Aim: The fatty acid-binding protein 2 (FABP2) A54T polymorphism has been associated with type 2 diabetes mellitus (T2DM) and obesity in many but not all studies. Our aim was to investigate possible associations of FABP2 A54T polymorphism with T2DM and/or obesity in a Greek Caucasian population. Methods: 242 subjects with T2DM and 188 control subjects were genotyped for the FABP2 A54T polymorphism using PCR-RFLP method. Of the total subjects included in both groups, 172 were classified as obese (BMI ≥30kg/m2) and 258 were classified as nonobese (BMI <30kg/m2). Results: In the whole population, 218 subjects (50.7%) were genotyped as AA, 175 subjects (40.7%) as AT, and 37 subjects (8.6%) as TT for the FABP2 A54T polymorphism. According to the dominant model, the frequency of AA genotype was significantly lower in obese than in nonobese subjects (43.0% vs 55.8%, p =0.009). No significant difference was observed in genotypes between diabetic and nondiabetic subjects. According to the additive model, the presence of TT genotype was significantly associated with obesity after adjusting for age, sex, and the presence of T2DM (OR 2.32, p =0.028). Conclusion: FABP2 A54T polymorphism may help identify Caucasian subjects at risk for obesity. [Copyright &y& Elsevier]

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]

Abstract: The threonine (Thr) for alanine (Ala) codon 54 polymorphism of the fatty acid binding protein (FABP) 2 gene, when compared to the wild type, is associated with dyslipidemia. Since dyslipidemia is common in diabetes and is associated with increased cardiovascular risk, we tested the hypothesis that Thr-54 is associated with increased cardiovascular risk in patients with diabetes. The secondary prevention veterans affairs HDL intervention trial (VA-HIT) was carried out in patients with dyslipidemia. The DNA of trial participants (n =776) was screened for the Thr-54 polymorphism and cardiovascular endpoints were monitored. The polymorphism was detected in 370 (47.7%). For first occurrence of the primary endpoint [myocardial infarction (MI) or coronary heart disease (CHD) death] the hazard ratio (HR) and confidence intervals (Cox proportional hazards model) was 2.5 (1.2, 5.3) p =.02 in diabetic carriers of Thr-54 versus carriers without diabetes or fasting glucose >7mmol/L. For the expanded endpoint (stroke, MI or CHD death), the corresponding HR was 3.0 (1.4, 5.4) p =.0003 and for the stroke alone the corresponding HR was 3.5 (1.4–8.9) p =.01. The higher cumulative incidence of the expanded endpoint in diabetic participants carrying the FABP2 polymorphism versus non-diabetic carriers was consistently present throughout the 5 years of the study (p =.0002). We conclude that based on the VA-HIT data, the Thr-54 polymorphism of the FABP2 gene is associated with a 2–3.5-fold increase in cardiovascular risk in dyslipidemic men with diabetes compared to their non-diabetic counterparts. [Copyright &y& Elsevier]

Abstract: Hypertriglyceridemia and dietary lipids have been suggested to modulate the severity of alcoholic liver disease and the progression to alcoholic cirrhosis (AC). The intestinal fatty acid binding protein (IFABP) is the main transporter of dietary fatty acids into the enterocyte and has a genetic polymorphism, FABP2 A54T that has been associated with hypertriglyceridemia. We determined the frequency of the FABP2 gene polymorphism using PCR-RFLP and measured serum triglycerides, HDL, LDL, total lipids and cholesterol in 67 patients with AC and in 124 unrelated healthy individuals. Frequencies of genotypes and alleles were similar between the two groups. The healthy subjects, who were homozygous for the Thr54 genotype had significantly higher mean triglyceride serum concentrations than those homozygous for the Ala54 genotype (P <0.05). However, AC patients who were homozygous for the Thr54 genotype, had lower mean triglyceride serum concentrations (P <0.01), and had a significantly longer period of continued alcohol abuse prior to the diagnosis of liver cirrhosis compared to the AC patients homozygous for the Ala54 genotype (P <0.05). Our data suggests that the polymorphism Thr54 of the FABP2 gene is associated with a later onset of AC in the lower economic status Mexican population studied. [Copyright &y& Elsevier]

The alanine (A) to threonine (T) substitution at codon 54 of the intestinal fatty acid-binding protein 2 (FABP2) has been associated with dyslipidaemia and other characteristics of the metabolic syndrome, which in turn is a risk factor for cerebrovascular disease. The aim of this study was to investigate whether the A54T polymorphism in the FABP2 gene is associated with internal carotid artery (ICA) stenosis in stroke patients. Swedish subjects initially diagnosed with acute cerebrovascular disease (n = 196) that had been assessed with ultrasound of the carotid arteries were identified and grouped depending on whether a stenosis was found. The subjects were genotyped for the A54T polymorphism using a PCR-RFLP method. In a multivariate logistic-regression analysis, where known risk factors for atherosclerosis were fixed (diabetes, systolic blood pressure, age and smoking), having the FABP2 T allele was a significant risk factor for ICA stenosis (odds ratio 2.9; 95% confidence interval, 1.1–7.7; p = 0.04) together with diabetes (odds ratio 4.9; 95% confidence interval, 1.8–14; p < 0.01). Age, smoking and blood pressure did not reach statistical significance. In conclusion, our result supports the hypothesis that the FABP2 A54T polymorphism is associated with ICA stenosis. [ABSTRACT FROM AUTHOR]

Wanby P, Palmquist P, Rydén I, Brattström L, Carlsson M. The FABP2 gene polymorphism in cerebrovascular disease.Acta Neurol Scand 2004 DOI: 10.1111/j.1600-0404.2004.00335.x© Blackwell Munksgaard 2004.Earlier studies have shown that the fatty acid binding protein 2 (FABP2) T54 allele is associated with dyslipidemia, which in turn correlates with the incidence of cerebrovascular disease (CVD). To assess whether the FABP2 gene A54T polymorphism is associated with an increased risk of CVD we undertook a case–control study.A total of 407 patients diagnosed with acute CVD and 158 control subjects were genotyped for the A54T polymorphism using a PCR-RFLP method.Allele and genotype frequencies of the FABP2 A54T polymorphism did not differ between subjects with acute CVD (TT, 9.6%; TA, 41.0%; AA, 49.4%) and controls (TT, 7.6%; TA, 41.1%; AA, 51.3%;P = ns) or in the following subgroups of CVD compared with controls: non-cardioembolic infarction (n = 252), intracerebral hemorrhage (n = 23), and cardioembolic infarction (n = 91). In transient ischemic attacks (TIAs) (n = 41) the combined TT and TA genotype frequency (TT + TA, 65.9%) was more frequent than in controls (48.7%) (P = 0.05). Furthermore, the TT genotype was more frequent in non-smoking patients under the age of 70 (n = 77) with a non-cardioembolic infarction (TT, 18.2%) compared with controls (7.6%) (P = 0.024).Our findings suggest an involvement of the FABP2 (A54T) gene polymorphism in the pathogenesis of CVD. The FABP2 T54 allele appears to be a genetic susceptibility marker for TIA and non-cardioembolic infarction at younger onset. [ABSTRACT FROM AUTHOR]

The intestinal fatty acid-binding protein (I-FABP) shows binding specificity for long-chain fatty acids and is proposed to be involved in uptake of dietary fatty acids and their intracellular transport. We have determined the sequence of the gene encoding I-FABP in zebrafish. The zebrafish I-FABP gene contains four exons interrupted by three introns. Radiation hybrid mapping assigned the I-FABP gene to linkage group 1. A 924 bp sequence 5′ upstream of the initiation codon in the I-FABP gene contained several putative cis-acting regulatory elements. In adult zebrafish, reverse transcription-polymerase chain reaction (RT-PCR) detected I-FABP mRNA in intestine, brain, liver, muscle and testis. Quantitative RT-PCR demonstrated that I-FABP mRNA was most abundant in intestine, followed by brain. I-FABP mRNA levels were very low in muscle, testis, heart, liver, skin and ovary. RT-PCR using total RNA extracted from zebrafish embryos detected I-FABP mRNA as early as 12 h post-fertilization. Whole-mount in situ hybridization to zebrafish embryos detected I-FABP mRNA in the yolk syncytial layer (YSL) at early somitogenesis. Later during embryonic development the I-FABP mRNA was detected in the intestinal bulb, liver and pancreas primordium. Expression in YSL, liver or pancreas has not been previously reported for fish or mammalian I-FABP genes and may be related to specific physiological differences between fishes and mammals. [Copyright &y& Elsevier]

In a double-blind parallel-group study, serum lipids and visceral fat/total fat ratio in young women (n=49) with variants of lipid transporters, i.e., fatty acid binding protein 2 (FABP2) and microsomal triglyceride transfer protein (MTP), were analyzed by substituting dietary triacylglycerol (TAG) with sn-1,3-diacylglycerol (DAG). All subjects, including some with the hyperlipidemia-prone genotypes Ala54Thr of FABP2 and c-493g of MTP, received DAG or TAG (20 g/day) for 8 weeks. Reductions of serum lipids from weeks 4 to 8 in FABP2–Ala54Thr heterozygotes and MTP -493g homozygotes were significantly different between the DAG and TAG groups (p<0.05, p<0.01). Visceral fat/total fat (%), as determined by computed tomography (CT), was lower in FABP2–Ala54Thr heterozygotes (p<0.05) of the DAG group. The apoCII/CIII ratio was higher in the DAG group than in the TAG group (p<0.01). Other variants of lipid metabolism, including peroxisome proliferator activated receptors (PPARs) α and γ and SREBP cleavage-activating protein (SCAP), were only slightly affected by dietary DAG. Conclusion: improvement of serum lipid profiles and visceral fat/total fat ratio (CT) was potentiated by DAG intake in subjects with hyperlipidemia-prone genotypes (Ala54Thr heterozygotes of FABP2 and -493g homozygotes of MTP). [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]

Aims/hypothesis. An Ala54Thr polymorphism in the FABP2 gene has previously been associated with insulin resistance and lipid oxidation rates in Pima Indians. Ala54Thr functionally alters the protein’s ability to bind and transport dietary fatty acids. In the current report, we sought additional functional variation in FABP2 by sequencing putative regulatory regions. Methods. More than 1.2 Kb of the putative promoter of FABP2 was sequenced in 20 Pima subjects. Variations were genotyped in 84 additional Pima Indian subjects to assess haplotype combinations. Functional activities of variant and nonvariant promoters were compared in Caco-2 cells transfected with luciferase reporter constructs. Results. Seven variations were identified in the FABP2 promoter in Pima Indians. Genotypes of these variants were in complete concordance with each other, and were in complete concordance with Ala54Thr. Therefore, only two promoter alleles were observed in Pima Indians, an Ala54-associated promoter and a Thr54-associated promoter. In contrast, genotyping of these variants in Caucasian DNA showed multiple genotypic combinations. In vitro reporter assays indicated that the Thr54-associated promoter in Pima Indians resulted in a threefold reduction in promoter activity as compared to Ala54-associated promoter. Conclusion/interpretation. Two functional variations exist in FABP2—the coding Ala54Thr and the variant promoter. In the Pima Indian population, but not the Caucasian population, these two functional variants are always carried on the same allele. Therefore, some of the in vivo phenotypic associations previously attributed to the Ala54Thr substitution, which alters binding characteristics of the protein, could instead be due to promoter variation, which alters expression levels. [ABSTRACT FROM AUTHOR]