Association of the fto fat mass and obesityassociated. The fto gene was identified in 2007 in a genomewide association study which looked at over 35,000 people to determine genes involved in obesity. A common variant in the fto gene is associated with body. Research article open access fto gene polymorphisms.
Obesity, attributable to the interaction of genetic makeup, lifestyle and environment factors are a multifactorial disease. However, not all people with similar genetics or same environmental setup become obese. A variation in the fto gene linked to obesity appears to have more to do with eating a lot, rather than being less active, a scottish study shows. Association between fat mass and obesity associated fto. Frayling and coworkers reported a strong and robust association between a single nucleotide polymorphism snp located within the first fto intron rs9939609 and bmi, which concurred with the results of two independent studies published. The fto gene is one of the most recently studied genes zlatohlavek et al. The pathogenesis of obesity is reportedly related to variations in the fat mass and an obesityassociated gene fto. A commonly carried allele of the obesityrelated fto gene. Inactivation of the fto gene protects from obesity. Mutations within the gene fto have been implicated as the strongest genetic determinant of obesity risk in humans, but the mechanism behind this. The human fto gene is located on chromosome 16 and expressed in a wide range of tissues, including the adipose tissue and specific areas of. The pathogenesis of obesity is reportedly related to variations in the fat mass and an obesity.
Common fto fat mass and obesity associated gene variants have recently been associated with body mass index bmi and obesity in several large studies. Associations between obesity candidate gene polymorphisms. Several other studies have also observed associations between fto. Several other studies have also observed associations between fto variants and obesityrelated traits in various. Given that fto regulates d23r signaling in mice, we tested in humans whether variants in fto would interact with a variant in the ankk1 gene, which alters d2r signaling. Knowing your family history can help you understand your risk for obesity and obesityrelated conditions like diabetes and heart disease. A recently identified variant within the fat mass and obesityassociated fto gene is carried by 46% of western europeans and is associated with an 1. Role of rs9939609fto gene variant in weight loss, insulin. Role for the obesityrelated fto gene in the cellular sensing of amino acids pawan gulatia,b,1, man ka cheunga,b. Assessing genetreatment interactions at the fto and. Fto is one of the genes known to contribute to polygenic obesity.
The distribution of fat mass and obesityassociated gene fto genes rs9939609 and rs1421085 in obese and normal ethnic mongolians was. The fto gene harbors variation with the strongest effect on adiposity and obesity risk. Pdf the fat mass and obesity associated fto gene is a newly identified genetic factor for obesity. To date, however, knowledge on the mechanisms coupling variants in the intron of the fto gene to its expression or enzymatic activity to alter metabolism remains scarce. Recent studies from genomewide associated studies reveal that genetic variants in the fto gene are associated not only with human adiposity and metabolic disorders, but also with cancer. To widen the geographical coverage of the fto studies, we have analyzed the association between the fto gene variant rs17817449 gc and obesity in a slavic eastern european population. Analysis of the obesity gene fto in 14,803 type 1 diabetes cases and controls. Snps in the first intron of the fat mass and obesity related. The connection between fto and diabetes was lost after correcting for bodymass index, suggesting that fto mediated susceptibility to type 2 diabetes. The genetic factors predisposing to obesity are poorly understood.
Polymorphisms within the fto gene have consistently been associated with obesity across multiple populations. Variations in the human fto gene have been linked to obesityrelated traits in several genomewide association studies. Please use one of the following formats to cite this article in your essay, paper or report. Other nonheme iron enzymes function to reverse alkylated dna and rna damage by oxidative demethylation. Here, we show by bioinformatics analysis that fto shares sequence motifs with feii and 2oxoglutaratedependent oxygenases. In fact it was the first one to be identified by genome wide association.
Genomewide association studies gwas for bmi, waisttohip ratio, and other adiposity traits have identified more than 300 singlenucleotide polymorphisms snps. Testing for the fto gene and other genes can be performed practically, but it is not very helpful because the treatment interventions are the same for individuals with and without the fto gene. Associations between obesity candidate gene polymorphisms fat mass and obesityassociated fto, melanocortin4 receptor mc4r, leptin lep and leptin receptor lepr and dietary intake in pregnant women volume 120 issue 4 maisa c. Within the pfkp gene, rs6602024 showed very strong association with bmi p 4. We conducted a combined analysis of 16,094 boys and girls aged 118 years from 14 studies to examine the following. While the exact mechanism remains to be unraveled, it has been shown that genetic variants within the fto gene are linked functionally to another obesity related gene called irx3, which promotes. Although there is reason to hope that these discoveries will eventually lead to new preventive and therapeutic agents for obesity, this will take time because such developments require detailed mechanistic understanding of how an. Pdf understanding the fat gene obesity common variant. Fat mass and obesity associated fto gene influences. Relationship between fat mass and obesityassociated fto gene. However, to date, it is not known whether the association between genetic variation in fto and obesity is mediated through effects on energy intake or energy expenditure. With 1 billion overweight and 300 million obese persons worldwide, it is crucial to understand the implications of carrying this very common allele for. The researchers noticed the fto gene variation when they screened the genes of nearly 2,000 diabetes patients and almost 3,000 people without diabetes in. Obesity is a serious international health problem that increases the risk of several common diseases.
Variations in the fat mass and obesityassociated fto gene are linked to obesity. The fto gene and obesity in a large eastern european population sample. We find that recombinant murine fto catalyzes the feii and 2ogdependent demethylation of 3methylthymine in singlestranded dna, with. Pmid 18159244 the earlier study also had conclusions with regard to another gene. A genomewide search for type 2 diabetessusceptibility genes identified a common variant in the fto fat mass and obesity associated gene that predisposes to diabetes through an effect on body mass index bmi. Dietary intake, fto genetic variants, and adiposity.
Nih people who carry a variant in the socalled obesity gene, fto, react just as well to diet and exercise as those without it, a research. These changes could have a significant impact on the risk of obesity related morbidity in the general population. We identified a set of snps in the first intron of the fto fat mass and obesity associated gene on chromosome 16q12. Research article open access fto gene polymorphisms and obesity risk.
Until recently, the investigation of the molecular function of fto had not led to conclusive results. The fto rs9939609 have been previously associated with energy and macronutrient intake the present study evaluates the association between specific eating behavior scores and fto polymorphism in chilean children. Role for the obesityrelated fto gene in the cellular. An obesitypredisposing variant of the fto gene regulates. A cluster of single nucleotide polymorphisms snps in the first intron of the fat mass and obesity related fto gene were the first common variants discovered to be associated with body mass. Fat mass and obesityassociated gene fto is associated. The studies in mice and humans indicate that the fto gene plays a role in nervous and cardiovascular systems and has a strong association with body mass index, obesity risk, and type 2 diabetes. The obesityassociated fto gene encodes a 2oxoglutarate. Common genetic variation in obesity, lipid transfer genes.
Fto gene study fto fat gene the fto genotype rs9939609 has been termed the fat gene. The fto gene is involved in overweight and obesity, about 42% caucasians, 5% africans and 21% asians carry risk variants for overeating. D fat mass and obesity associated gene fto the fto gene was identified as an important locus harboring common variants with an unequivocal impact on obesity predisposition and fat mass at the population level. The fto gene rs9939609 obesityrisk allele and loss of control over eating marian tanofskykraff.
Pdf a cluster of single nucleotide polymorphisms snps in the first intron of the fat mass and obesity related fto gene were the first common. Variations in the human fto gene have been linked to obesity and altered connectivity of the dopaminergic neurocircuitry. The first report linking the fto fat mass and obesityassociated gene and obesity came from a genomewide association study linking fto variants with type 2 diabetes in a european population. This is because it encodes an enzyme fat mass and obesityassociated protein, also known as alphaketoglutaratedependent dioxygenase fto that is positively linked to obesity. Another report fingers rs1121980 within the fto gene as having the strongest association to early onset obesity compared to several other snps all in the same linkage block. Genomewide association study identified the fat mass and obesityassociated fto gene as an obesity susceptibility gene frayling. In the present study, we propose a model of interactions between genetic vulnerabilityrepresented by fat mass and obesityassociated fto geneand stable psychopathological traits, such as bodily disorders and emotion dysregulation for eds patients.
Inactivation of the fto gene protects from obesity nature. However, the exact molecular mechanisms responsible for the effect of fto on obesity remain largely unknown. Physical activity and the association of common fto gene. A common variant in the fto gene is associated with body mass index and predisposes to childhood and adult obesity. The role of lifestyle factors such as physical activity in those with an underlying fto genetic predisposition is unknown.
Previous data support a role for fto variation in influencing food intake. Fto gene rs9939609 obesityrisk allele and loss of control. The fto gene and obesity in a large eastern european. Obesityassociated fto gene variant is associated with obesity. Pdf numerous classical genetic studies have proved that genes are contributory factors for obesity. For full access to this pdf, sign in to an existing account, or purchase an annual subscription. Genome wide association studies undoubtedly linked variants of the fat mass and obesityassociated protein fto to obesity. Fto gene variants have been associated with obesity phenotypes in sedentary and obese populations, but rarely with skeletal muscle and elite athlete phenotypes. But just identifying the gene didnt explain why it was so widely linked to higher bmi as well as an increased risk of adhd, depression, and dementia.
In addition, adiposity appeared to mediate the association between fto variant and the risk of type 2 diabetes 2,3. This gene is a nuclear protein of the alkb related nonhaem iron and 2oxoglutaratedependent oxygenase superfamily but the exact physiological function of this gene is not known. Genomewide association scan shows genetic variants in the. In addition, some reports have claimed ethnicspecific associations with alternative snps, and to. The most convincing findings to date for an obesity related genotype have been for variants at the fat mass and obesity associated fto gene. Variation in fto contributes to childhood obesity and. An obesityassociated fto gene variant and increased. Frayling tm, timpson nj, weedon mn, zeggini e, freathy rm, lindgren cm, et al. A functional correlation is now reported between fto, the equivalent gene in. Role of variants of fto gene in obesity certain variants of the fto. The fto gene has not been previously implicated in obesity, but it maps to a region where linkage to bmi has been reported in two previous genomewide linkage scans lod 3. Fto gene were the first common variants discovered to be associated with body mass index and.
Obesity and genetics nature nurture obesity medicine. We found that rs9939609a allele of the fto gene is associated with eating behavior traits that may predispose obese children to increased energy intake and obesity. The fat mass and obesity associated fto gene is a newly identified genetic factor for obesity. Studies in mice and humans indicate a role in nervous and. Pdf the fto gene and obesity in a large eastern european. An obesityassociated fto gene variant and energy intake in children n engl j med 359. Obesity associated genetic variation in fto is associated. Here, we report that fat mass and obesityassociated protein fto in. Background variation in the fat mass and obesityassociated fto gene has provided the most robust associations with common obesity to date. Eating disorders eds show a multifactorial etiopathogenesis including environmental, psychological and biological factors. Variants in the fto fat mass and obesity associated gene are associated with increased body mass index in humans. In a recent genomewide association study, frayling et al. In 1089 participants, comprising 530 elite rugby athletes and 559 nonathletes, dna was collected and genotyped for the fto rs9939609 variant using realtime pcr.
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