FTO

Protein:

Fat mass and obesity-associated protein

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Fat mass and obesity-associated protein (FTO) is an enzyme which interacts with RNA molecules and is thought to influence expression of proteins, it is encoded for by the FTO gene. FTO has been termed the “obesity gene” in popular culture due to a variety of studies which described and association between certain SNPs and increased body mass 1.

Exactly how FTO influences body mass is under debate with two differing hypotheses. Some describe a direct activity; in rats FTO expression in the brain was shown to be increased following dietary restriction 2. This gave rise to the hypothesis that levels of FTO regulate hunger, and that the risk SNPs in FTO may lead to increased expression, even when full leading to further eating and increased weight gain.

However, another hypothesis disputes this pointing out that the SNPs associated with FTO do not actually alter the protein function or activity and rather influence expression of another gene IRX3 (iroquious homeobox protein 3). Over-expression of IRX3 associated with the SNPs within FTO leads to changes in fat metabolism, promoting its storage rather than its breakdown and also reduces the energy generating activity of mitochondria in fat cells.

It is not clear if either (or both) hypotheses are correct, although numerous studies are underway to attempt to improve our understanding.

G76373A

Science Grade
B+
Gastrointestinal Health
rsID Number Major Allele Minor Allele Minor Allele Frequency (%)
rs1121980 g a 37

Risk Description

The risk allele ‘A’ (sometimes reported as ‘T’) of G76373A in the FTO gene has been associated with an earlier onset of obesity, compared to several other associated SNPs. For those carrying a single copy of the ‘A’ allele a large scale study showed a 1.67x risk for developing obesity, which increased to 2.76x for those with two ‘A’ alleles 4.

Carriers of a single ‘A’ also weighed on average 1.2 kg (2.6 lb) more than those with no copies; while those carrying two ‘A’ alleles weighed on average 3 kg (6.6 lb) more 5. As discussed above the exact mechanism linking FTO and obesity together is poorly understood and may in fact be linked to the activity of another gene. However, G76373A acts as an excellent marker.

Interestingly there are several SNPs in the FTO gene which associate together, which are sometimes all grouped together under the SNP ID rs9930506 5. We’ve chosen to focus on rs1121980 alone as this SNP was found to demonstrate the strongest effect 4. The other SNPs are listed below briefly but the important information is included in this section.

Nutritional Contraindications:*

Ingredient Active Ingredient Effect
High fat or sugar diet

As the exact mechanisms linking SNPs in FTO with obesity are unknown it is not possible to provide targeted nutritional advice. However, those carrying risk alleles in any of the SNPs described on this page should take particular care to ensure they do not consume too many dietary fats or sugars.

Discuss this information with your doctor before taking any course of action.

G67694A

Science Grade
B+
Gastrointestinal Health
rsID Number Major Allele Minor Allele Minor Allele Frequency (%)
rs9939973 g a 35

Risk Description

The risk allele ‘A’ of G67694A in the FTO gene has been associated with the development of obesity in association with several other SNPs. As these SNPs are so closely associated they are often inherited together and the effects are highly similar. Therefore all information supplied above for G76373A (rs1121980) is applicable here.

Discuss this information with your doctor before taking any course of action.

T77812C

Science Grade
B+
Gastrointestinal Health
rsID Number Major Allele Minor Allele Minor Allele Frequency (%)
rs7193144 t c 31

Risk Description

The risk allele ‘C’ of T77812C in the FTO gene has been associated with the development of obesity in association with several other SNPs. As these SNPs are so closely associated they are often inherited together and the effects are highly similar. Therefore all information supplied above for G76373A (rs1121980) is applicable here.

Discuss this information with your doctor before taking any course of action.

G67880A

Science Grade
B+
Gastrointestinal Health
rsID Number Major Allele Minor Allele Minor Allele Frequency (%)
rs9940128 g a 35

Risk Description

The risk allele ‘A’ of G67880A in the FTO gene has been associated with the development of obesity in association with several other SNPs. As these SNPs are so closely associated they are often inherited together and the effects are highly similar. Therefore all information supplied above for G76373A (rs1121980) is applicable here.

Discuss this information with your doctor before taking any course of action.

C83401A

Science Grade
B+
Gastrointestinal Health
rsID Number Major Allele Minor Allele Minor Allele Frequency (%)
rs8050136 c a 32

Risk Description

The risk allele ‘A’ of C83401A in the FTO gene has been associated with the development of obesity in association with several other SNPs. As these SNPs are so closely associated they are often inherited together and the effects are highly similar. Therefore all information supplied above for G76373A (rs1121980) is applicable here.

Discuss this information with your doctor before taking any course of action.

T87653A

Science Grade
B+
Gastrointestinal Health
rsID Number Major Allele Minor Allele Minor Allele Frequency (%)
rs9939609 t a 34

Risk Description

The risk allele ‘A’ of T87653A in the FTO gene has been associated with the development of obesity in association with several other SNPs. As these SNPs are so closely associated they are often inherited together and the effects are highly similar. Therefore all information supplied above for G76373A (rs1121980) is applicable here.

Discuss this information with your doctor before taking any course of action.

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