The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Stefan Schreiber - One of the best experts on this subject based on the ideXlab platform.
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The effect of FABP2 promoter haplotype on response to a diet with medium-chain triacylglycerols
Genes & Nutrition, 2012Co-Authors: Diana Rubin, Ulf Helwig, Maria Pfeuffer, Annegret Auinger, Andreas Ruether, Dennis Matusch, Stephanie Darabaneanu, Sandra Freitag-wolf, Michael Nothnagel, Stefan SchreiberAbstract: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.
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the effects of retinol on postprandial parameters in men with different FABP2 promoter haplotypes
Hormone and Metabolic Research, 2007Co-Authors: U Helwig, Diana Rubin, Stefan Schreiber, Frank Doring, J Kiosz, W Bitter, Ulrich R Folsch, J SchrezenmeirAbstract:The fatty acid binding protein 2 (FABP2) mediates the intestinal uptake of fatty acids. We and others have identified six FABP2 promoter polymorphisms which result in two haplotypes, A and B. Reporter-gene assays indicated different activity in FABP2 promoter alleles A and B and different responsiveness to PPAR ligands. IN SILICO analysis revealed different putative binding sites in FABP2 haplotypes for retinoid-dependent transcription factors. Therefore, we assumed that retinol supplementation may effect postprandial fat uptake differently in men with FABP2 promoter haplotype A and B. To test this hypothesis, we administered 5000 I.U. retinol/day for 8 weeks to 19 homozygotes for AA and 21 homozygotes for BB and assessed the alteration of postprandial triglycerides during this intervention. FABP2 genotype groups did not significantly differ in anthropometric and laboratory parameters. The alteration of postprandial triglycerides did not differ significantly between genotypes during intervention. This also held true after adjustment for BMI. Furthermore, in a subgroup which had a combination of promoter and common exon polymorphism, the alteration of the postprandial triglycerides did not differ between genotypes. In conclusion, the postprandial triglyceride metabolism of FABP2 promoter AA and BB did not respond differently to retinol administration even though IN SILICO analysis suggested this.
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association between functional FABP2 promoter haplotype and type 2 diabetes
Hormone and Metabolic Research, 2006Co-Authors: Eva Fisher, Stefan Schreiber, Maja Klapper, H Boeing, A Pfeiffer, Jochen Hampe, Barbara Burwinkel, J Schrezenmeir, Frank DoringAbstract:Fatty acid-binding protein 2 (FABP2) is a cytosolic protein expressed exclusively in epithelial cells of the small intestine. Some, albeit not conclusive, evidence indicates that the Thr-allele of FABP2 Ala54Thr polymorphism is associated with type 2 diabetes. More recently, common FABP2 promoter polymorphisms have shown association with postprandial increase of triglycerides, body composition and plasma lipid levels. Therefore, we reasoned that variants in the FABP2 promoter may also predispose to type 2 diabetes mellitus. In our Caucasian study population, we found three SNPs and three insertion-deletion polymorphisms that are in complete linkage disequilibrium defining promoter haplotype A and B within 1kb 5' of the FABP2 initiation codon. Haplotype calculations indicated that the FABP2 promoter and Ala54Thr variants were strongly linked. Functional analysis of promoter fragments demonstrated that haplotype difference is caused by polymorphisms within 260 bp downstream of the FABP2 initiation codon. Using a prospective case-control study nested within the EPIC-Potsdam cohort of 192 incident type 2 diabetes cases and 384 sex-/age-matched controls, male subjects carrying the FABP2 haplotype B allele showed significantly decreased risk of type 2 diabetes when adjusted for BMI (OR = 0.50, 95 % CI = 0.28 - 0.87, p < 0.05) and additional covariates (OR = 0.42, 95 % CI 0.22 - 0.81, p < 0.01). Further adjustment for the Ala54Thr polymorphism revealed an OR of 0.18 (95 % CI 0.06 - 0.49, p < 0.001). Similarly, Ala/Ala homozygote males carrying the promoter haplotype B had decreased risk (0.33, 0.11 - 0.94, p < 0.05) of type 2 diabetes after stratification for the Ala54Thr polymorphism. FABP2 promoter haplotypes or genotype combinations defined by the promoter and Ala54Thr polymorphism were not associated with BMI, body fat, leptin, HbA (1c), total cholesterol or HDL. In conclusion, our findings suggest that the functional FABP2 promoter haplotype may contribute to type 2 diabetes in a sex-specific manner.
Frank Doring - One of the best experts on this subject based on the ideXlab platform.
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association between functional FABP2 promoter haplotypes and body mass index analyses of 8072 participants of the kora cohort study
Molecular Nutrition & Food Research, 2009Co-Authors: Mike Bohme, Maja Klapper, Frank Doring, Harald Grallert, Christian Gieger, Alexandra Fischer, Iris M Heid, Herich Wichmann, Thomas IlligAbstract:Studies in relatively small cohorts provide preliminary evidence that functional fatty acid binding protein 2 (FABP2) promoter haplotypes are associated with type 2 diabetes and BMI. Here, we studied the influence of the haplotypes on BMI by using 8072 male and female participants of the Kooperative Gesundheitsforschung in der Region Augsburg (KORA) cohort. By linear regression analysis, we found in males a reduction of -0.39 BMI units (95% CI: -0.73, -0.05, p = 0.024) in homozygous FABP2 promoter haplotype B carriers. Carriers of haplotype B showed a significant decrease in BMI of -0.19 BMI units (95% CI: -0.35, -0.02, p = 0.027). In accordance, a significant reduction in BMI of the minor haplotype carriers in the BMI point categories of 25-30 (BMI units: -0.10, 95% CI: -0.18, -0.01, p = 0.03) and < 30 (BMI units: -0.37, 95% CI: -0.67, -0.07, p = 0.02) were found. In summary, the minor FABP2 promoter haplotype B contributes to a reduced BMI in men. This provides evidence that functional FABP2 contributes to multifactorialy regulated body weight.
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analysis of the transcriptional regulation of the FABP2 promoter haplotypes by pparγ rxrα and oct 1
Biochimica et Biophysica Acta, 2008Co-Authors: Mike Bohme, Inke Nitz, Frank Doring, Maja KlapperAbstract: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.
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transcriptional regulation of the fatty acid binding protein 2 FABP2 gene by the hepatic nuclear factor 1 alpha hnf 1α
Gene, 2008Co-Authors: Maja Klapper, Mike Bohme, Inke Nitz, Frank DoringAbstract:Abstract The human fatty acid binding protein ( FABP2 ) is involved in intestinal absorption and intracellular trafficking of long-chain fatty acids. Here we investigate transcriptional regulation of FABP2 by the endodermal hepatic nuclear factor 1 alpha (HNF-1α). In electromobility shift and supershift assays we show the presence of two adjacent HNF-1α binding sites within the FABP2 promoter regions -185 to -165 and -169 to -149. HNF-1α activates an FABP2 promoter luciferase construct by 3.5 and 20-fold in Caco-2 and Hela cells, respectively. Mutational analysis of HNF-1α elements resulted in about 50% reduction of basal and HNF-1α induced activity of FABP2 promoter constructs, predominantly caused by deletion of the -185 to -165 site. Thus, our data suggest a major role of HNF-1α in control of FABP2 expression in intestine via a functional HNF-1α recognition element within FABP2 promoter region -185 to -165.
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the effects of retinol on postprandial parameters in men with different FABP2 promoter haplotypes
Hormone and Metabolic Research, 2007Co-Authors: U Helwig, Diana Rubin, Stefan Schreiber, Frank Doring, J Kiosz, W Bitter, Ulrich R Folsch, J SchrezenmeirAbstract:The fatty acid binding protein 2 (FABP2) mediates the intestinal uptake of fatty acids. We and others have identified six FABP2 promoter polymorphisms which result in two haplotypes, A and B. Reporter-gene assays indicated different activity in FABP2 promoter alleles A and B and different responsiveness to PPAR ligands. IN SILICO analysis revealed different putative binding sites in FABP2 haplotypes for retinoid-dependent transcription factors. Therefore, we assumed that retinol supplementation may effect postprandial fat uptake differently in men with FABP2 promoter haplotype A and B. To test this hypothesis, we administered 5000 I.U. retinol/day for 8 weeks to 19 homozygotes for AA and 21 homozygotes for BB and assessed the alteration of postprandial triglycerides during this intervention. FABP2 genotype groups did not significantly differ in anthropometric and laboratory parameters. The alteration of postprandial triglycerides did not differ significantly between genotypes during intervention. This also held true after adjustment for BMI. Furthermore, in a subgroup which had a combination of promoter and common exon polymorphism, the alteration of the postprandial triglycerides did not differ between genotypes. In conclusion, the postprandial triglyceride metabolism of FABP2 promoter AA and BB did not respond differently to retinol administration even though IN SILICO analysis suggested this.
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association between functional FABP2 promoter haplotype and type 2 diabetes
Hormone and Metabolic Research, 2006Co-Authors: Eva Fisher, Stefan Schreiber, Maja Klapper, H Boeing, A Pfeiffer, Jochen Hampe, Barbara Burwinkel, J Schrezenmeir, Frank DoringAbstract:Fatty acid-binding protein 2 (FABP2) is a cytosolic protein expressed exclusively in epithelial cells of the small intestine. Some, albeit not conclusive, evidence indicates that the Thr-allele of FABP2 Ala54Thr polymorphism is associated with type 2 diabetes. More recently, common FABP2 promoter polymorphisms have shown association with postprandial increase of triglycerides, body composition and plasma lipid levels. Therefore, we reasoned that variants in the FABP2 promoter may also predispose to type 2 diabetes mellitus. In our Caucasian study population, we found three SNPs and three insertion-deletion polymorphisms that are in complete linkage disequilibrium defining promoter haplotype A and B within 1kb 5' of the FABP2 initiation codon. Haplotype calculations indicated that the FABP2 promoter and Ala54Thr variants were strongly linked. Functional analysis of promoter fragments demonstrated that haplotype difference is caused by polymorphisms within 260 bp downstream of the FABP2 initiation codon. Using a prospective case-control study nested within the EPIC-Potsdam cohort of 192 incident type 2 diabetes cases and 384 sex-/age-matched controls, male subjects carrying the FABP2 haplotype B allele showed significantly decreased risk of type 2 diabetes when adjusted for BMI (OR = 0.50, 95 % CI = 0.28 - 0.87, p < 0.05) and additional covariates (OR = 0.42, 95 % CI 0.22 - 0.81, p < 0.01). Further adjustment for the Ala54Thr polymorphism revealed an OR of 0.18 (95 % CI 0.06 - 0.49, p < 0.001). Similarly, Ala/Ala homozygote males carrying the promoter haplotype B had decreased risk (0.33, 0.11 - 0.94, p < 0.05) of type 2 diabetes after stratification for the Ala54Thr polymorphism. FABP2 promoter haplotypes or genotype combinations defined by the promoter and Ala54Thr polymorphism were not associated with BMI, body fat, leptin, HbA (1c), total cholesterol or HDL. In conclusion, our findings suggest that the functional FABP2 promoter haplotype may contribute to type 2 diabetes in a sex-specific manner.
Maja Klapper - One of the best experts on this subject based on the ideXlab platform.
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association between functional FABP2 promoter haplotypes and body mass index analyses of 8072 participants of the kora cohort study
Molecular Nutrition & Food Research, 2009Co-Authors: Mike Bohme, Maja Klapper, Frank Doring, Harald Grallert, Christian Gieger, Alexandra Fischer, Iris M Heid, Herich Wichmann, Thomas IlligAbstract:Studies in relatively small cohorts provide preliminary evidence that functional fatty acid binding protein 2 (FABP2) promoter haplotypes are associated with type 2 diabetes and BMI. Here, we studied the influence of the haplotypes on BMI by using 8072 male and female participants of the Kooperative Gesundheitsforschung in der Region Augsburg (KORA) cohort. By linear regression analysis, we found in males a reduction of -0.39 BMI units (95% CI: -0.73, -0.05, p = 0.024) in homozygous FABP2 promoter haplotype B carriers. Carriers of haplotype B showed a significant decrease in BMI of -0.19 BMI units (95% CI: -0.35, -0.02, p = 0.027). In accordance, a significant reduction in BMI of the minor haplotype carriers in the BMI point categories of 25-30 (BMI units: -0.10, 95% CI: -0.18, -0.01, p = 0.03) and < 30 (BMI units: -0.37, 95% CI: -0.67, -0.07, p = 0.02) were found. In summary, the minor FABP2 promoter haplotype B contributes to a reduced BMI in men. This provides evidence that functional FABP2 contributes to multifactorialy regulated body weight.
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analysis of the transcriptional regulation of the FABP2 promoter haplotypes by pparγ rxrα and oct 1
Biochimica et Biophysica Acta, 2008Co-Authors: Mike Bohme, Inke Nitz, Frank Doring, Maja KlapperAbstract: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.
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transcriptional regulation of the fatty acid binding protein 2 FABP2 gene by the hepatic nuclear factor 1 alpha hnf 1α
Gene, 2008Co-Authors: Maja Klapper, Mike Bohme, Inke Nitz, Frank DoringAbstract:Abstract The human fatty acid binding protein ( FABP2 ) is involved in intestinal absorption and intracellular trafficking of long-chain fatty acids. Here we investigate transcriptional regulation of FABP2 by the endodermal hepatic nuclear factor 1 alpha (HNF-1α). In electromobility shift and supershift assays we show the presence of two adjacent HNF-1α binding sites within the FABP2 promoter regions -185 to -165 and -169 to -149. HNF-1α activates an FABP2 promoter luciferase construct by 3.5 and 20-fold in Caco-2 and Hela cells, respectively. Mutational analysis of HNF-1α elements resulted in about 50% reduction of basal and HNF-1α induced activity of FABP2 promoter constructs, predominantly caused by deletion of the -185 to -165 site. Thus, our data suggest a major role of HNF-1α in control of FABP2 expression in intestine via a functional HNF-1α recognition element within FABP2 promoter region -185 to -165.
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promoter variants and transcriptional regulation of the intestinal fatty acid binding protein gene FABP2
2007Co-Authors: Maja KlapperAbstract:The human intestinal fatty acid binding protein (FABP2) is a cytosolic 15 kDa protein and is involved in resorption of long-chain fatty acids. Phenotyping of FABP2 knock-out mice and association analysis of promoter haplotypes revealed FABP2 as a susceptibility gene for insulin resistance and related traits. Relevant FABP2 promoter polymorphisms -80Del>T, -136AGTAG>Del, -168AAG>T, -260G>A, -471G>A, and -778G>T result in two haplotypes A and B. Haplotype B possesses 2-3 fold lower transcriptional activity than A in Caco-2 cells. The aim of this work was to investigate the general and haplotype-specific transcriptional regulation of the human FABP2 promoter. For this purpose, reporter gene assays in human colonic carcinoma Caco-2, cervix carcinoma Hela and hepatoma Huh7 cells, site-directed mutagenesis, electrophoretic mobility shift assays and supershift-assays were used. Data show that FABP2 is strongly activated by the transcriptional factor HNF-1a and HNF-4a via identified functional recognition elements within FABP2 promoter region -185/-165 and -336/-324, respectively. This seems to be of importance in the control of FABP2 expression by differentiation and nutrients, e.g. dietary lipids. Furthermore it was demonstrated that polymorphism -80Del>T, together with -136AGTAG>Del and -168AAG>T, essentially determines different activities of FABP2 promoter haplotypes. GATA factors bind less efficiently to the –80B allele compared to A. This results in two-fold lower activation of haplotype B by these factors. GATA factors play a major role in development and differentiation and therefore very likely mediate a differential activation of FABP2 promoter haplotypes also in-vivo. Taken together, the work provides insights into the molecular basis of the general and variant specific transcriptional regulation of the diabetes type 2 associated human FABP2 gene.
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association between functional FABP2 promoter haplotype and type 2 diabetes
Hormone and Metabolic Research, 2006Co-Authors: Eva Fisher, Stefan Schreiber, Maja Klapper, H Boeing, A Pfeiffer, Jochen Hampe, Barbara Burwinkel, J Schrezenmeir, Frank DoringAbstract:Fatty acid-binding protein 2 (FABP2) is a cytosolic protein expressed exclusively in epithelial cells of the small intestine. Some, albeit not conclusive, evidence indicates that the Thr-allele of FABP2 Ala54Thr polymorphism is associated with type 2 diabetes. More recently, common FABP2 promoter polymorphisms have shown association with postprandial increase of triglycerides, body composition and plasma lipid levels. Therefore, we reasoned that variants in the FABP2 promoter may also predispose to type 2 diabetes mellitus. In our Caucasian study population, we found three SNPs and three insertion-deletion polymorphisms that are in complete linkage disequilibrium defining promoter haplotype A and B within 1kb 5' of the FABP2 initiation codon. Haplotype calculations indicated that the FABP2 promoter and Ala54Thr variants were strongly linked. Functional analysis of promoter fragments demonstrated that haplotype difference is caused by polymorphisms within 260 bp downstream of the FABP2 initiation codon. Using a prospective case-control study nested within the EPIC-Potsdam cohort of 192 incident type 2 diabetes cases and 384 sex-/age-matched controls, male subjects carrying the FABP2 haplotype B allele showed significantly decreased risk of type 2 diabetes when adjusted for BMI (OR = 0.50, 95 % CI = 0.28 - 0.87, p < 0.05) and additional covariates (OR = 0.42, 95 % CI 0.22 - 0.81, p < 0.01). Further adjustment for the Ala54Thr polymorphism revealed an OR of 0.18 (95 % CI 0.06 - 0.49, p < 0.001). Similarly, Ala/Ala homozygote males carrying the promoter haplotype B had decreased risk (0.33, 0.11 - 0.94, p < 0.05) of type 2 diabetes after stratification for the Ala54Thr polymorphism. FABP2 promoter haplotypes or genotype combinations defined by the promoter and Ala54Thr polymorphism were not associated with BMI, body fat, leptin, HbA (1c), total cholesterol or HDL. In conclusion, our findings suggest that the functional FABP2 promoter haplotype may contribute to type 2 diabetes in a sex-specific manner.
J Schrezenmeir - One of the best experts on this subject based on the ideXlab platform.
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the effects of retinol on postprandial parameters in men with different FABP2 promoter haplotypes
Hormone and Metabolic Research, 2007Co-Authors: U Helwig, Diana Rubin, Stefan Schreiber, Frank Doring, J Kiosz, W Bitter, Ulrich R Folsch, J SchrezenmeirAbstract:The fatty acid binding protein 2 (FABP2) mediates the intestinal uptake of fatty acids. We and others have identified six FABP2 promoter polymorphisms which result in two haplotypes, A and B. Reporter-gene assays indicated different activity in FABP2 promoter alleles A and B and different responsiveness to PPAR ligands. IN SILICO analysis revealed different putative binding sites in FABP2 haplotypes for retinoid-dependent transcription factors. Therefore, we assumed that retinol supplementation may effect postprandial fat uptake differently in men with FABP2 promoter haplotype A and B. To test this hypothesis, we administered 5000 I.U. retinol/day for 8 weeks to 19 homozygotes for AA and 21 homozygotes for BB and assessed the alteration of postprandial triglycerides during this intervention. FABP2 genotype groups did not significantly differ in anthropometric and laboratory parameters. The alteration of postprandial triglycerides did not differ significantly between genotypes during intervention. This also held true after adjustment for BMI. Furthermore, in a subgroup which had a combination of promoter and common exon polymorphism, the alteration of the postprandial triglycerides did not differ between genotypes. In conclusion, the postprandial triglyceride metabolism of FABP2 promoter AA and BB did not respond differently to retinol administration even though IN SILICO analysis suggested this.
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association between functional FABP2 promoter haplotype and type 2 diabetes
Hormone and Metabolic Research, 2006Co-Authors: Eva Fisher, Stefan Schreiber, Maja Klapper, H Boeing, A Pfeiffer, Jochen Hampe, Barbara Burwinkel, J Schrezenmeir, Frank DoringAbstract:Fatty acid-binding protein 2 (FABP2) is a cytosolic protein expressed exclusively in epithelial cells of the small intestine. Some, albeit not conclusive, evidence indicates that the Thr-allele of FABP2 Ala54Thr polymorphism is associated with type 2 diabetes. More recently, common FABP2 promoter polymorphisms have shown association with postprandial increase of triglycerides, body composition and plasma lipid levels. Therefore, we reasoned that variants in the FABP2 promoter may also predispose to type 2 diabetes mellitus. In our Caucasian study population, we found three SNPs and three insertion-deletion polymorphisms that are in complete linkage disequilibrium defining promoter haplotype A and B within 1kb 5' of the FABP2 initiation codon. Haplotype calculations indicated that the FABP2 promoter and Ala54Thr variants were strongly linked. Functional analysis of promoter fragments demonstrated that haplotype difference is caused by polymorphisms within 260 bp downstream of the FABP2 initiation codon. Using a prospective case-control study nested within the EPIC-Potsdam cohort of 192 incident type 2 diabetes cases and 384 sex-/age-matched controls, male subjects carrying the FABP2 haplotype B allele showed significantly decreased risk of type 2 diabetes when adjusted for BMI (OR = 0.50, 95 % CI = 0.28 - 0.87, p < 0.05) and additional covariates (OR = 0.42, 95 % CI 0.22 - 0.81, p < 0.01). Further adjustment for the Ala54Thr polymorphism revealed an OR of 0.18 (95 % CI 0.06 - 0.49, p < 0.001). Similarly, Ala/Ala homozygote males carrying the promoter haplotype B had decreased risk (0.33, 0.11 - 0.94, p < 0.05) of type 2 diabetes after stratification for the Ala54Thr polymorphism. FABP2 promoter haplotypes or genotype combinations defined by the promoter and Ala54Thr polymorphism were not associated with BMI, body fat, leptin, HbA (1c), total cholesterol or HDL. In conclusion, our findings suggest that the functional FABP2 promoter haplotype may contribute to type 2 diabetes in a sex-specific manner.
Diana Rubin - One of the best experts on this subject based on the ideXlab platform.
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The effect of FABP2 promoter haplotype on response to a diet with medium-chain triacylglycerols
Genes & Nutrition, 2012Co-Authors: Diana Rubin, Ulf Helwig, Maria Pfeuffer, Annegret Auinger, Andreas Ruether, Dennis Matusch, Stephanie Darabaneanu, Sandra Freitag-wolf, Michael Nothnagel, Stefan SchreiberAbstract: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.
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the effects of retinol on postprandial parameters in men with different FABP2 promoter haplotypes
Hormone and Metabolic Research, 2007Co-Authors: U Helwig, Diana Rubin, Stefan Schreiber, Frank Doring, J Kiosz, W Bitter, Ulrich R Folsch, J SchrezenmeirAbstract:The fatty acid binding protein 2 (FABP2) mediates the intestinal uptake of fatty acids. We and others have identified six FABP2 promoter polymorphisms which result in two haplotypes, A and B. Reporter-gene assays indicated different activity in FABP2 promoter alleles A and B and different responsiveness to PPAR ligands. IN SILICO analysis revealed different putative binding sites in FABP2 haplotypes for retinoid-dependent transcription factors. Therefore, we assumed that retinol supplementation may effect postprandial fat uptake differently in men with FABP2 promoter haplotype A and B. To test this hypothesis, we administered 5000 I.U. retinol/day for 8 weeks to 19 homozygotes for AA and 21 homozygotes for BB and assessed the alteration of postprandial triglycerides during this intervention. FABP2 genotype groups did not significantly differ in anthropometric and laboratory parameters. The alteration of postprandial triglycerides did not differ significantly between genotypes during intervention. This also held true after adjustment for BMI. Furthermore, in a subgroup which had a combination of promoter and common exon polymorphism, the alteration of the postprandial triglycerides did not differ between genotypes. In conclusion, the postprandial triglyceride metabolism of FABP2 promoter AA and BB did not respond differently to retinol administration even though IN SILICO analysis suggested this.
