Postprandial responses of individual fatty acids in subjects homozygous for the threonine- or alanine-encoding allele in codon 54 of the intestinal fatty acid binding protein 2 gene

Ågren, Jyrki; Vidgren, Helvi M.; Valve, Raisa S.; Laakso, Markku; Uusitupa, Matti

doi:10.1093/ajcn/73.1.31

Cited by 57 publications

(34 citation statements)

References 20 publications

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“…The possible mechanism through which the A54T polymorphism causes renal disease has not been established but might be related to endothelial dysfunction and glomerular damage due to higher levels of saturated fatty acids. Moreover, this polymorphism has also been associated with insulin resistance (19 -21) and higher levels of triglycerides in the fasting state and after a fatty meal challenge (18,22). In the present study, the association of the TT genotype with elevated triglycerides was only evident among patients without renal function impairment (serum creatinine Ͻ1.5 mg/dl).…”

Section: Discussionsupporting

confidence: 46%

“…The A54T polymorphism of the FABP2 gene has been associated with an increase in FABP2 affinity for longchain fatty acids such as stearic and palmitic acids and consequently with higher levels of these fatty acids after a test meal (18). We have previously reported that patients with type 2 diabetes and microalbuminuria had higher levels of saturated fatty acids, especially stearic and palmitic acids, than normoalbuminuric patients (12).…”

Section: Discussionmentioning

confidence: 98%

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The Fatty Acid–Binding Protein-2 A54T Polymorphism Is Associated With Renal Disease in Patients With Type 2 Diabetes

Canani

Capp

et al. 2005

Diabetes

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The intestinal fatty-acid binding protein-2 (FABP2) gene codes a protein responsible for the absorption of longchain fatty acids. To test whether FABP2 is a candidate gene for renal disease in patients with type 2 diabetes, a functional A54T polymorphism was genotyped in 1,042 Brazilians with type 2 diabetes. Patients were classified as having normoalbuminuria (urinary albumin excretion [UAE] <20 g/min; n ‫؍‬ 529), microalbuminuria (UAE 20 -199 g/min; n ‫؍‬ 217), or proteinuria (UAE >199 g/ min; n ‫؍‬ 160). Patients with end-stage renal disease (ESRD) (n ‫؍‬ 136) were also included. D iabetic nephropathy develops in up to 40% of diabetic patients at most, even when high glucose levels are maintained for long periods of time (1). Epidemiological (2) and familial (3-5) studies have demonstrated that genetic susceptibility contributes to the development of diabetic nephropathy in both type 1 and type 2 diabetes. The precise genetic model underlying diabetic nephropathy susceptibility is uncertain, but several genes with a minor effect have been associated with diabetic nephropathy (6). Insulin resistance has been implicated in the development of diabetic nephropathy (7), and aggregation of components of the metabolic syndrome is associated with a high prevalence of diabetic nephropathy (8). The intestinal fatty acidbinding protein-2 (FABP2) gene codes a protein expressed in enterocytes and is responsible for the absorption of long-chain fatty acids (9). A single nucleotide polymorphism (SNP) in the FABP2 gene at codon 54 causes an amino acid change (Ala 3 Thr). This change affects the ability of the protein to bind and transport dietary fatty acids (9). Serum saturated fatty acids might induce endothelial dysfunction (10) and are related to increased cardiovascular mortality (11). We have previously reported increased levels of serum saturated fatty acids in patients with type 2 diabetes and microalbuminuria (12), as well as a reduction in albumin excretion rate after replacement of red meat (high content of saturated fatty acids) with chicken (low content of saturated fatty acids) in these patients (13). Based on these observations, we hypothesized that genetically predisposed subjects exposed to a diet with a high content of saturated fatty acids might be at high risk for developing renal disease. Therefore, we decided to examine whether FABP2 is a susceptibility gene for renal disease in patients with type 2 diabetes. Our study focused particularly on the A54T polymorphism, since this polymorphism results in a functionally altered FABP2 protein. Additional information for this article can be found in an online appendix at http://diabetes.diabetesjournals.org. RESEARCH DESIGN AND METHODSESRD, end-stage renal disease; FABP2, fatty acid-binding protein-2; IHD, ischemic heart disease; SNP, single nucleotide polymorphism; UAE, urinary albumin excretion.

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Section: Discussionsupporting

confidence: 46%

Section: Discussionmentioning

confidence: 98%

The Fatty Acid–Binding Protein-2 A54T Polymorphism Is Associated With Renal Disease in Patients With Type 2 Diabetes

Canani

Capp

et al. 2005

Diabetes

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“…In the latter study, Pima Indians may have other genetic predispositions to develop insulin resistance. In oral fatloading tests in adults, the postprandial response of 14-18-carbon FAs in chylomicron and VLDL triacylglycerols was significantly elevated in Thr54 homozygotes, whereas the amount of 20-and 22-carbon PU- 29) . In the high-fat meal test, plasma insulin level was significantly higher immediately after the meal in Thr54 subjects, although there were no significant differences in either glucose or triglyceride responses 28) .…”

Section: Discussionmentioning

confidence: 88%

Thr-encoding Allele Homozygosity at Codon 54 of FABP 2 Gene May be Associated with Impaired Delta 6 Desatruase Activity and Reduced Plasma Arachidonic Acid in Obese Children

Okada

Furuhashi-Sato

Kuromori

et al. 2006

JAT

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Background: Alanine-for-threonine substitution at codon 54 (A54T polymorphism) in the fatty acid-binding protein 2 gene (FABP2) has been associated with hypertriglyceridemia and insulin resistance. Impairment in the activity of delta 6 and 5 desaturases is also supposed to be a factor predisposing the development of insulin resistance syndrome. Aim: We investigated the relationship between A54T polymorphism in FABP2 and the impairment of long-chain polyunsaturated fatty acid metabolism in obese children. Methods: Thirty-two obese children participated. During the study, the children continued their habitual diet, which was documented in a 3-day food record using household measures. Anthropometry was performed, and serum lipid and fatty acid composition in plasma were analyzed. The polymorphism of codon 54 in the FABP 2 gene was analyzed. Results: The allele frequency was 0.66 and 0.34 for Ala54 and Thr54, respectively. There were no significant differences in age, body mass index, fasting serum glucose, insulin or serum lipoproteins among the three polymorphism groups. These were also no significant differences in the intake of energy, the percentage of energy nutrients or in the dietary lipid composition. The content of arachidonic acid (AA) in plasma was lowest in Thr/Thr54 (p 0.05). The indices of delta-6 desaturase (D6D) activity in Thr/Thr54 were significantly lower than in Thr/Ala54 or Ala/Ala54 (p 0.05, p 0.01, respectively). Conclusions: In obese children, Thr/Thr54 of the FABP 2 gene is associated with impaired activation of D6D and reduced AA content. The results in the LCPUFA profile suggest that Thr/Thr54 may predispose the to development of insulin resistance.

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“…In our study, the elevation of CRP in individuals with Thr allele could be related to an altered postprandial re- [31] . Elevated free fatty acids increase the accumulation of triglycerides in the adipocyte, related with imbalance of lipoprotein lipase activity and overproduction of adipokines such as IL-6 inducing high levels of CRP [32] .…”

Section: Discussionmentioning

confidence: 50%

Polymorphism Ala54Thr of Fatty Acid-Binding Protein 2: Allelic Frequencies and Influence on Cardiovascular Risk Factors in a Multicenter Study of Castilla y Leon

Luis¹,

Ballesteros²,

Ruiz³

et al. 2010

Ann Nutr Metab

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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.

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Postprandial responses of individual fatty acids in subjects homozygous for the threonine- or alanine-encoding allele in codon 54 of the intestinal fatty acid binding protein 2 gene

Abstract: The threonine-encoding allele of the FABP2 gene is associated with an increased postprandial response of 14-18-carbon fatty acids but not with changes in the relative amounts of individual fatty acids introduced to chylomicron triacylglycerols.

Cited by 57 publications

References 20 publications

The Fatty Acid–Binding Protein-2 A54T Polymorphism Is Associated With Renal Disease in Patients With Type 2 Diabetes

The Fatty Acid–Binding Protein-2 A54T Polymorphism Is Associated With Renal Disease in Patients With Type 2 Diabetes

Thr-encoding Allele Homozygosity at Codon 54 of FABP 2 Gene May be Associated with Impaired Delta 6 Desatruase Activity and Reduced Plasma Arachidonic Acid in Obese Children

Polymorphism Ala54Thr of Fatty Acid-Binding Protein 2: Allelic Frequencies and Influence on Cardiovascular Risk Factors in a Multicenter Study of Castilla y Leon

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