Disease relevance of FABP2

• These results suggest that in African-Americans, these variants in the IRS-1 and FABP2 genes are not associated with the risk of type 2 diabetes, severe obesity, or marked hyperinsulinemia, but that their independent and joint effects may be associated with small increases in BMI [1].
• It is proposed that, in the absence of confounding factors such as environmental and genetic variables, the FABP2 polymorphism has an important effect on postprandial lipids in vivo, potentially influencing plasma levels of lipids and atherogenesis [2].
• Our objectives were to determine whether Ala54Thr FABP2 and G-493T MTP polymorphisms are associated with increased risks of insulin resistance syndrome (IRS) in youth and/or modify the expression of accompanying dyslipidemia [3].
• Our study suggests that the effects of FABP2 allelic variations on lipid traits are context dependent, indicating that this variant may play an important role in cardiovascular pathogenesis in the presence of IRS or hypertriglyceridemia [3].
• Moreover, there was no significant relationship between FABP2 alleles and lipoprotein diameter or the prevalence of coronary heart disease in both genders [4].

Psychiatry related information on FABP2

• It was concluded that FABP2 genotype influences insulin sensitivity independent of body composition, habitual physical activity levels, and HRT status in postmenopausal white women [5].

High impact information on FABP2

• Since the FABP2 threonine-encoding allele was found to be associated with insulin resistance and increased fat oxidation in vivo, we further analyzed the FABP2 gene products for potential functional differences [6].
• The intestinal fatty acid binding protein locus (FABP2) was investigated as a possible genetic factor in determining insulin action in the Pima Indian population [6].
• A polymorphism at codon 54 of FABP2 was identified that results in an alanine-encoding allele (frequency 0.71) and a threonine-encoding allele (frequency 0.29) [6].
• Experimental studies have suggested rat intestinal fatty acid-binding protein (I-FABP) as a serum marker reflecting bowel ischemia; the present study evaluates the human homologue (human I-FABP) as a serum marker for the diagnosis of acute ischemic diseases of the bowel [7].
• All 5 patients with mesenteric infarction showed I-FABP levels of > 100 ng/mL [7].

Chemical compound and disease context of FABP2

• We investigated 1022 Tongan subjects, 433 men and 589 women aged 15-85 years, to identify possible associations between the FABP2 Ala54Thr polymorphism, obesity, Type II diabetes, BMI, glucose tolerance and standard lipid variables [8].
• BACKGROUND: The 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 [9].
• An alanine to threonine substitution at codon 54 of the fatty acid binding protein 2 (FABP2) gene has been associated with insulin resistance in Pima Indians and with obesity in aboriginal Canadians [10].

Biological context of FABP2

• Allele frequencies of Gly972Arg IRS-1 and Ala54Thr FABP2 were 0.07 and 0.22, respectively; there were no differences in allele or genotype frequencies between patients and control subjects for either gene variant [1].
• Based on titration microcalorimetry and Caco-2 cell line transfection studies, it has been suggested that the A54T of the FABP2 gene plays a significant role in the assimilation of dietary fatty acids [2].
• Trinucleotide repeat polymorphism at the human intestinal fatty acid binding protein gene (FABP2) [11].
• Genetic variants in the intestinal fatty acid-binding protein-2 (FABP2) gene have been associated with body composition phenotypes [12].
• We also present novel evidence that genetic variation in the FABP2 gene may increase susceptibility to stroke [13].

Anatomical context of FABP2

• We examined the association between the Ala(54)Thr variant in the FABP2 gene and levels of visceral (VAT) and sc (SAAT) abdominal fat in a group of 223 premenopausal African-American (n = 103) and Caucasian (n = 120) women [12].
• FABP2, the intestinal-type FABP, is expressed exclusively in enterocytes in the small intestine [14].
• In conclusion, Thr54 allele of FABP2 has associations with lower adjusted resting metabolic rate, resistance in reducing visceral white adipose tissue (WAT) and early onset of obesity in Japanese obese women [15].
• In subjects with coronary artery disease (CAD+), the prevalence of FABP-2 54TT genotype was higher (16.5% versus 5.2%) and that of ABCA1 219RK and KK genotypes lower (33.0% versus 51.5%) than in subjects with no CAD [16].
• Moreover, it appears that the Ala to Thr substitution at residue 54 of the human IFABP does not alter the fundamental mechanism of ligand transfer to membranes, but nevertheless causes a consistent decrease in the rate of transfer [17].

Associations of FABP2 with chemical compounds

• Our data clearly document that the A54T polymorphism of FABP2 specifically influences small intestinal lipid absorption without modifying glucose uptake or metabolism [2].
• FABP2 genotype was not associated with fasting or postprandial lipemia test triacylglycerol or free fatty acids (P >/= 0.22 for all), but postprandial lipid oxidation rates were higher (P = 0.01), which suggests that fat absorption is higher in Thr54 carriers than in Ala54 homozygotes [18].
• In summary, we have confirmed the association of the FABP2 T54 allele with increased concentrations of cholesterol and triglycerides in genotype-discordant sibling pairs [13].
• Among the metabolic components of IRS, only triglyceride (TG) displayed an interaction with FABP2 polymorphism: compared with Thr/Ala and Ala/Ala, the Thr/Thr genotype was associated with a steeper increase in TC, LDL-C, and apoB parallel to TG concentrations (P <0.001) [3].
• CONCLUSIONS: An adverse combination of common alleles of the FABP-2, APOE, and PPARgamma genes in women increases their TG concentrations to values comparable to those seen in men [19].

Physical interactions of FABP2

• Finally, both cis-parinaric acid and cis-parinaroyl CoA were much less ordered in the I-FABP ligand binding site than with L-FABP [20].
• PYY induced expression of tetraspanins and intestinal fatty acid binding protein (I-FABP) may be part of a mechanism whereby FFA modulate expression of differentiation dependent proteins in the mucosa [21].
• Mutation of this HNF-4 binding site abolished the luciferase reporter activity of hFABP2 in postconfluent Caco-2 cells [22].

Regulatory relationships of FABP2

• Similarly, hydrocortisone and insulin enhanced the cellular content of I- and L-FABP whereas leptin triggered I-FABP expression only after an 8-hour incubation [23].
• BACKGROUND: The affinity of intestinal fatty acid binding protein (FABP) for fatty acids is regulated by the polymorphism at codon 54 of the FABP2 gene (alanine-to-threonine shift) [24].

Other interactions of FABP2

• Allelic frequencies in 70 controls and 110 patients with diabetes from the Chennai Urban Population Study were 52.9% for FABP2 Thr54, 73.0% for APOC3 -482T, and 80.2% for APOC3 -455C [25].
• Also, very modest genotype-phenotype associations were observed between APOE genotype (P = 0.016) and plasma low-density lipoprotein cholesterol concentration and between FABP2 genotype and plasma 2-h postprandial, glucose concentration (P = 0.048) [26].
• In women only, both GNB3 825C>T and FABP2 A54T genotypes were significantly associated with HTGW (OR 2.02, 95% CI 1.01, 4.05 and OR 1.95, 95% CI 1.01, 3.74, respectively) [27].
• Polymorphism of the fatty acid-binding protein 2 (FABP2) gene has been shown to affect the affinity of intestinal FABP for fatty acids [28].
• Most NIDDM result from polygenic heredity, and susceptibility genes conducive to increased receptivity to deleterious environmental influences are now under investigation, such as beta 3 adrenergic receptor, FABP2 and OB [29].

Analytical, diagnostic and therapeutic context of FABP2

• OBJECTIVE: We tested the hypothesis that, in sedentary nondiabetic subjects following a low-fat diet, Thr54 FABP2 carriers have lower glucoregulatory function, greater postprandial lipemia, and greater lipid oxidation rates than do their Ala54 FABP2-homozygous counterparts [18].
• DISCUSSION: Serum I-FABP levels do not predict clinical intestinal allograft rejection [30].
• MATERIALS AND METHODS: I-FABP was repetitively measured in nine intestinal transplant recipients and correlated with findings of surveillance endoscopy [30].
• DESIGN AND METHODS: I-FABP and L-FABP were measured with specific immunoassays in autopsy samples of the intestine (duodenum, jejunum, ileum and colon) of 23 subjects and in plasma samples from patients (n = 51) with intestinal and/or hepatic disease [31].
• No significant association was obtained between the polymorphism of the FABP2 gene and body mass index [32].

References