Body Key

Body key (Amway)

2 protein vázající mastné kyseliny (FABP2) Ala54Thr (rs1799883) = rs1799883 Fatty acid binding protein 2 (FABP2) Ala54Thr

Funkce proteinu

• Involvement in the intracellular binding, transport, and metabolism of FFA [5]
• FABP2 might be involved in regulating food intake and intestinal FA utilization [5]
• Increased intestinal b-oxidation due to higher FABP2 expression in people with the common alleles of promoter and exon polymorphism
• Might reduce serum FFA and by that improve insulin sensitivity and prevent dyslipidemia [5]

Porucha funkce proteinu

• FABP2 gene deletion in mice
• Increased weight gain [5]
• Higher circulating TGs [5]

Lokalizace proteinu

• Mature enterocytes of the small intestine [5]
• Marginal amounts have been identified in the stomach and large intestine in rodents [5]

Vliv polymorfismu rs1799883

• FAB2 - variations in the promoter (haplotypes A/B) and exon 2 (Ala54Thr) are associated with dyslipidemia and insulin resistanc [5]
• The Thr-54-allele is linked to the described promoter haplotype B [5]
• Only participants who were homozygous for both allele B and the Thr54-allele had higher concentrations of postprandial triglycerides and insulin [5]
• The G to A polymorphism (rs1799883) of codon 54 results in the substitution of threonine (Thr) for alanine (Ala) [4]
• Increases strongly with latitude (p < 0.01) [PMID 18282109OA-icon.png] [2]

• 2-fold greater binding affinity for long-chain fatty acids [6]
• Identification of four gene variants associated with myocardial infarction. [PMID 16175505OA-icon.png] [2]
• Association of genetic variants with atherothrombotic cerebral infarction in Japanese individuals with metabolic syndrome. [PMID 18506375] [2]
• Association of genetic variants with chronic kidney disease in Japanese individuals with type 2 diabetes mellitus. [PMID 19288030]
• Associated with increased susceptibility to T2DM risk among Asians but not Caucasians [4]
• Soluble fibre (Plantago ovata husk) reduces plasma low-density lipoprotein (LDL) cholesterol, triglycerides, insulin, oxidised LDL and systolic blood pressure in hypercholesterolaemic patients: A randomised trial. [PMID 20413122] [2]
• Identification of type 2 diabetes-associated combination of SNPs using support vector machine. [PMID 20416077OA-icon.png] [2]
• Population based allele frequencies of disease associated polymorphisms in the Personalized Medicine Research Project. [PMID 20565774OA-icon.png] [2]
• Gene Polymorphisms of ADIPOQ +45T>G, UCP2 -866G>A, and FABP2 Ala54Thr on the Risk of Colorectal Cancer: A Matched Case-Control Study [PMID 23826253OA-icon.png] [2]
• Moderate effects of apple juice consumption on obesity-related markers in obese men: impact of diet-gene interaction on body fat content and may influence weight management . [PMID 22038464] [2]
• Associated with phenotypes directly related to cold tolerance. Since variation in climate may be correlated with other aspects of environmental variation, it is possible that some of the signals that we detected reflect selective pressures other than climate [3]
• Associated with dyslipidemia, insulin resistance, and obesity [5]
• Potential association with concentrations of orexigenic glucose-dependent insulinotropic polypeptide (GIP) [5]
• Thr54-allele of the Ala54Thr polymorphism was associated with a higher food intake in Japanese [5]
• Lower activity of the FABP2 Ala54-variant might result in increases of GIP and energy intake [5]
• Higher serum FFA in Thr54-allele carriers [5]
• Higher binding affinity for the Thr54-allele to LCFA
• Enhanced absorption of fat and cholesterol
• May account for higher LDL-C and postprandial triglycerides [5]
• Lower concentrations of HDL-C [5]
• Obesity as well as higher leptin levels among women [6]
• Non-esterified fatty acids (NEFA) were 20% higher 7 hours after a high-fat meal in 54Thr/Thr homozygote subjects compared with 54Ala/Ala homozygotes [6]
• After fat ingestion, the 54Thr allele was also found to be associated with increased levels of postprandial triglycerides [6]
• After test meals enriched with trans- fatty acids relative to a similar meal enriched with cis-fatty acids showed that subjects with at least one copy of the Thr54 allele exhibited a greater increase in postprandial glucose levels and lipogenesis compared to those homozygous for the Ala54 allele [6]
• A group of obese, non-diabetic patients analyzed before and 3 months after a lifestyle modification program, consisting of hypocaloric diet (1,520 kcal/day) and aerobic exercise three times per week, (de Luis DA et al, Ann Nutr Metab 50: 354-360, 2006) showed that carriers of the 54Thr allele (compared to the wild-type 54Ala/Ala homozygotes) failed to have a significant reduction in fat mass, LDL-cholesterol levels, and leptin levels. [6]

Which factors determine FABP2 expression in human mucosa ? [5]

Vyšší exprese FABP2

• May have stimulated mitochondrial b-oxidation and intestinal FA utilization
• May reduce FA availability in the circulation [5]

• Correlated with (n-3) fatty acid (FA) intake in AA homozygotes (promotor mutation)
• Higher in AA homozygotes than in B-allele carriers after adjustment for (n-3) FA intake [5]
• (n-3) FA intake was more strongly associated with FABP2 expression than LCFA intake [5]
• Importance of dietary (n-3) FA in regulating FABP2 expression in AA homozygotes [5]
• Negatively correlated with serum FFA [5]
• 100% after 3 d of feed deprivation [5]
• Slightly increased after a high-fat diet [5]
• Unaltered by a 7-d fat feeding in mice [5]

Nižší exprese

• In lipid malabsorption syndromes in humans
• But not of FABP2 mRNA [5]
• Ala54Thr polymorphism
• More strongly associated with gene expression than promoter haplotypes [5]

Co bych řekla, že z toho plyne pro lidi s danou mutací...

• Snáz přibírají po tučném jídle, obzvláště bohatém na nasycené mastné kyseliny s dlouhým řetězcem
• Více se vyhýbat nekvalitním tukům (trans-MK a cis....?)
• Mají vyšší chuť k jídlu
• Hůře reagují na dietu
• V tomto ohledu na ně má menší regulační vliv konzumace omega-3 MK
• Ale pořád si myslím, že je o to důležitější...a především jejich vyšší poměr než množství
• Větší důraz na prevenci onemocnění ledvin, tlustého střeva, cév a vzniku diabetu

Receptor aktivovaný peroxizomovými proliferátory gama (PPARG nebo PPAR) Pro12Ala (rs1801282)

Beta-2 adrenergický receptor (ADRB2) Arg 16Gly (rs1042713)

Beta-2 adrenergický receptor (ADRB2) Gln27Glu (rs1042714)

Beta-3 adrenergický receptor (ADRB3) Arg64Trp (rs4994)

Literatura: