The association of fatty acid–binding protein 2 A54T polymorphism with postprandial lipemia depends on promoter variability

Helwig, Ulf; Rubin, Diana; Klapper, Maja; Li, Yin; Nothnagel, Michael; Fölsch, Ulrich R.; Döring, Frank; Schreiber, Stefan; Schrezenmeir, Jürgen

doi:10.1016/j.metabol.2006.11.014

Cited by 23 publications

(23 citation statements)

References 48 publications

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“…We and others could show that the rare haplotype B in the FABP2 promoter is associated with insulin resistance (Helwig et al 2007), type 2 diabetes (Formanack and Baier 2004;Li et al 2006) and hypercholesterolemia (Damcott et al 2003). Reporter gene assays indicated a higher responsiveness to PPARc/RXR of FABP2 promoter B versus promoter A.…”

Section: Introductionmentioning

confidence: 81%

“…Recent studies showed that the FABP2 promoter haplotype has some impact on postprandial lipemia, depending on the Thr54Ala exon polymorphism allele (Helwig et al 2007). It was shown that variation in the FABP2 promoter affects gene expression, which could have implications for prior association studies (Formanack and Baier 2004).…”

Section: Discussionmentioning

confidence: 99%

“…Subjects were recruited with regard to their FABP2 promoter haplotype carrier-ship from a prospective intervention cohort, and the details of the recruitment were described recently (Rubin et al 2010;Helwig et al 2007). …”

Section: Subjectsmentioning

confidence: 99%

“…Blood was collected in the fasting state, 0.5 h postprandially (pp) and hourly until 9 h after ingestion of a standardised lipid load (oMTT) (Helwig et al 2007;Rubin et al 2008). The oMTT with a liquid volume of 500 ml contained the following ingredients: 30 g of protein (11.9 kcal%), 75 g of carbohydrate (29.6 kcal%; 93% sucrose, 7% lactose), 58 g of fat (51.6 kcal%; 65% saturated, 35% unsaturated fatty acids), 10 g of alcohol (6.9 kcal%), 600 mg cholesterol and 30,000 IU retinylpalmitate.…”

Section: Laboratory Measurementsmentioning

confidence: 99%

“…FABP preferentially binds long-chain fatty acids (Lowe et al 1987;Richieri et al 1994) but also medium-chain fatty acids (Huang et al 2002), and its PPARc induced promoter activity is dependent on genetic variation (Helwig et al 2007). PPARc is upregulated by medium-chain fatty acids (Yonezawa et al 2004) and long-chain fatty acids itself and is therefore a target for gene-diet interaction studies.…”

Section: Introductionmentioning

confidence: 99%

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The effect of FABP2 promoter haplotype on response to a diet with medium-chain triacylglycerols

et al. 2012

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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 PPARc, which is upregulated by mediumchain fatty acids.

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Section: Introductionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Subjectsmentioning

confidence: 99%

Section: Laboratory Measurementsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The effect of FABP2 promoter haplotype on response to a diet with medium-chain triacylglycerols

et al. 2012

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Genetic polymorphism of fatty acid binding protein‐2 in hyperlipidemic Asian Indians in North India

Meena

Misra

Vikram

et al. 2022

American J Hum Biol

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Background Fatty acid binding protein‐2 (FABP‐2) is involved in the metabolism of lipids in the intestine. FABP‐2 Ala54Thr polymorphism involves a transition of G to A at codon 54 of FABP‐2, resulting in an amino acid substitution Ala54 to Thr54 and is associated with elevated fasting triglycerides in some hyperlipidemic populations. In current genome builds and gene databases the variant of the Ala54Thr FABP‐2 (rs 1 799 883) is annotated as c.163A>G (p. Thr55Ala). Aim and Objective The status of this polymorphism in hyperlipidemic Asian Indians from North India has not been investigated. This study was aimed to evaluate the distribution of the polymorphic variants of the Ala54Thr FABP‐2 and their association with lipids in hyperlipidemic subjects. Methods Ala54Thr FABP‐2 polymorphism in both hyperlipidemic (n = 210) and normolipidemic (n = 342) subjects was assessed by PCR‐RFLP. Results Ala54Thr genotypes and alleles distribution did not differ between the hyperlipidemic and normolipidemic groups. The heterozygous genotype FABP‐2 Ala/Thr was significantly associated with higher levels of triglycerides and very low‐density lipoproteins as compared to the homozygous variant (Thr/Thr) genotype and the wild type homozygous (Ala/Ala) genotype. Conclusions The heterozygous genotype FABP‐2 Ala54Thr is a risk factor for the development of hypertriglyceridemia and increased levels of VLDL‐c in Asian Indians from North India.

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Association of the fatty acid‐binding protein 2 gene Ala54Thr polymorphism with insulin resistance and blood glucose: a meta‐analysis in 13451 subjects

Zhao

Yang

2010

Diabetes Metabolism Res

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The association of fatty acid–binding protein 2 A54T polymorphism with postprandial lipemia depends on promoter variability

Cited by 23 publications

References 48 publications

The effect of FABP2 promoter haplotype on response to a diet with medium-chain triacylglycerols

The effect of FABP2 promoter haplotype on response to a diet with medium-chain triacylglycerols

Genetic polymorphism of fatty acid binding protein‐2 in hyperlipidemic Asian Indians in North India

Association of the fatty acid‐binding protein 2 gene Ala54Thr polymorphism with insulin resistance and blood glucose: a meta‐analysis in 13451 subjects

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