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Anyone heard of the FUT2 Gene and the link to poor B12 absorption?

PInk54 profile image
17 Replies

Hi everyone,

I thought people here might be interested in this...

I joined this site a few months ago as I suspected I had a B12 deficiency. Despite 'normal' range blood tests I was showing every sign of B12 deficiency, so have been supplementing and injecting regularly. I am starting to feel a little better.

In my search for answers, I signed up for DNA nutrition testing (I'm not sure if your rules let me name who it is with - so I won't for now). The findings confirmed my suspicion - it appears I have the G allee variant of the gene FUT2 which means that I don't absorb B12 well. Please see attached photo which was in my report which explains the gene and the variations. The same report also said that I was also 'likely to be low' on B6 and folate.

Has anyone heard of this gene? Does anyone here have it? I'd be interested to hear from anyone with any further information....

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PInk54 profile image
PInk54
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17 Replies
Gambit62 profile image
Gambit62Administrator

everyone will have the gene - that's the way gene's work. However there are a couple of variant forms of the gene that results in problems - so the question is really if someone knows they have one of the variants that causes problems

ncbi.nlm.nih.gov/clinvar/?t...]

unfortunately the table doesn't give any information on relative incidence of the variants.

and I'm not even going to pretend I understand all the details :)

fbirder profile image
fbirder

Promethease lists seven SNP locations for FUT(2). I am heterozygous for five of them.

Looking at the frequency charts for the, 6 SNPs that have them, the incidence of people without a mutation are:

30%, 30%, 20%, 30%, 30%, and 100%

So the chances of having no mutations at all are 0.3 x 0.3 x 0.2 x 0.3 x 0.3 x 1.0 = 0.00162 Which means that less than two people in 1000 do not have a mutation.

The reference you give doesn't say exactly which SNP they mean. Can you give the loaction (it'll be something like rs601338)?

fbirder profile image
fbirder

Hmmm, I did find something very interesting when looking at this... ncbi.nlm.nih.gov/pmc/articl...

These people have looked at the genetics of FUT(2) at one location - rs601338. They found that it influences the Active / inactive B12 in the blood. I've only read the abstract so far (and it's gin o'clock) so I'll try to understand the full thing tomorrow.

Gambit62 profile image
Gambit62Administrator in reply tofbirder

this article reports on some further research - no correlation to levels of Active B12 but does affect levels of B12 bound to haptocorrin

ncbi.nlm.nih.gov/pmc/articl...

PInk54 profile image
PInk54

Hi, many thanks for your comments. @fbirder, the SNP is rs602662.

I've copied the references that were added to the report. I haven't managed to read through them yet but they might help to shed more light.

References

Tanaka, T. (2009) ‘Genome-wide association study of vitamin B6, vitamin B12, folate, and homocysteine blood concentrations’, American Journal of Human Genetics, 84(4), pp. 477-482. ncbi.nlm.nih.gov/pmc/articl...

Hazra, A. et al. (2008) ‘Common variants of FUT2 are associated with plasma vitamin B12 levels’, Nature Genetics, 40(10), pp. 1160-1162. ncbi.nlm.nih.gov/pmc/articl...

National Centre for Biotechnology Information (2018). FUT2. ncbi.nlm.nih.gov/gene/2524

Tanwar VS. et al. (2013) ‘Common variant in FUT2 gene is associated with levels of vitamin B(12) in Indian population’, Gene, 515(1), pp. 224-8. ncbi.nlm.nih.gov/pubmed/232...

Carmel R., Perez-Perez GI., and Blaser MJ (1994) ‘Helicobacter pylori infection and food-cobalamin malabsorption’, Digestive diseases and sciences, 39(2), pp. 309-14 ncbi.nlm.nih.gov/pubmed/831...

Surendran S, et al (2018), ‘An update on vitamin B12-related gene polymorphisms and B12 status’, Genes & nutrition, 13:2. ncbi.nlm.nih.gov/pubmed/294...

fbirder profile image
fbirder

Thanks.

I, also, am heterozygous (A.G) for that SNP. As are 47% of europeans.

The 2018 paper looks very interesting. Looking at Table 1 for the rs602662 SNP I am struck by the different effect sizes found in the different studies. Of the 7 studies included in the analysis , 6 have effect sizes less than 1 pmol/L (or pg/mL) But the 7th has effect sizes of over 40 pg/mL

When I look elsewhere, I find that this particular SNP is associated with Systemic Lupus Erythematosus, Autoimmune Disease, Crohn's Disease, Ulcerative Colitis, Celiac Disease, Psoriasis, Ankylosing Spondylitis, Chronic Childhood Arthritis, Common Variable Immunodeficiency, Type I Diabetes Mellitus, Autoimmune Thyroid Disease and Vitamin B12 Measurement. selfdecode.com/snp/rs602662/

I'm not sure I'm going to worry even the tiniest bits about having the 'wrong' allele.

MoKayD profile image
MoKayD

This is really interesting information. I just checked my 23 and me raw data and found I have one copy of the variant gene for both rs602662 and rs601338. From what I understand (and I understand very little about the subject of genetics) having only one copy of a gene variant doesn't mean you will have a physical problem but you do have an increased risk of developing a problem.

PInk54 profile image
PInk54 in reply toMoKayD

Hmmm, interesting that MoKayD and fbirder and I have this gene variant and here we are -all B12 deficient. This can't be a co-incidence and personally, I'm not inclined to dismiss the evidence.

The exact wording on the report stated: Your genes indicate that you’re unlikely to be able to absorb vitamin B12 efficiently and therefore you're likely to have lower levels of B12 in your body.

fbirder - I just wondered where you read or how you conclude 47% of Europeans are heterozygous (A.G) for that SNP?....

fbirder profile image
fbirder in reply toPInk54

I really don't think you can say that it has any significance if two people have the same, very common, mutations. I'll bet there are another few thousand SNPs that we have in common.

If having the G allele for either of those SNPs influenced B12 to any extent then we would expect to see B12 deficiency more commonly in the Japanese. Their frequencies of homozygous G,G are 100% and 98.2%, respectively.

swmartin profile image
swmartin in reply tofbirder

Interesting that the Japanese range for B12 is so much higher than in the West

fbirder profile image
fbirder in reply toswmartin

It isn’t.

It is exactly the same - clancymedicalgroup.com/vita...

swmartin profile image
swmartin in reply tofbirder

According to the website that you linked:

"The medical field in Japan and Europe considers a patient to have vitamin B12 deficiency if testing reveals levels below 500 pg/mL to 550 pg/mL. Meanwhile, the low end of “normal” in America is 200pg/mL to 350 pg/mL."

And here in the UK, the average GP will insist that around 200 pg/ml is normal. Mainline Europe may be different / higher.

The last time I looked the top end of the Japanese range was 1500 pg/ml but in the UK it is 900 pg/ml (and the average GP would be 'hair on fire' panicking! seeing that level).

So not the same.

fbirder profile image
fbirder in reply toswmartin

The link was just to show that the interwebs are full of official-looking sites that are total and utter tommyrot and balderdash.

No, the bottom of the range isn't 500 in Europe. Nor is it 500 in Japan.

No, the top of the range isn't 900 is the UK. Here is my last result -

Serum vitamin B12 level (XE2pf) > 2,000 ng/L [180 - 640]

And here is the one from four years ago -

Serum vitamin B12 level (XE2pf) < 84 ng/L [150 - 883]

Don't believe all of what you read on the Interwebs.

fbirder profile image
fbirder in reply toMoKayD

It is more complicated than that. Being heterozygous (two copies) for a mutation can mean anything from no noticeable effect to being deadly. Most of the time the one mutated gene has little effect, if any. When it does have an effect the body can often compensate by getting the gene to make more of the protein.

If you load your 23andMe data into something called Promethease then you can get a lot of information. For the two SNPs you mention (for which I am also heterozygous) the percentage of people with a single mutation are 47% and 46%, respectively. That strongly suggests it's not associated with anything harmful - otherwise evolution would have got rid of it.

My reply was started after your previous post. But I seem to have anticipated the questions.

MoKayD profile image
MoKayD in reply tofbirder

Thank you for your response. I did some research when I discovered that I had a couple of the MTHFR gene variants. The little bit that I understood during my research reassured me that the probability of my gene variants causing me any problems with my health were statistically insignificant. I really wish the medical community would release a statement telling the general public that gene research is in it's infancy and much more research is needed before definitive medical advice can be given to people with gene variants.

Angel1x profile image
Angel1x

Sounds interesting are they still recruiting for testing

PurpleBoy profile image
PurpleBoy

Yes, I've heard of this. I've also read that, with certain variants of this, you can actually have high serum B12 but low functional B12. There are two proteins that carry B12--- one to the liver, and one to other tissues. For a certain gene, the liver one will work fine, but the one that delivers the B12 to other tissues doesn't deliver it properly so it can build up in the blood. As I recall it's holo-haptocorrin.

I myself have been trying to figure out why I have some symptoms of B12 deficiency but extremely high serum B12. This has been a laboratory finding over the course of three decades. My serum B12 level has never been below 850 and has been as high as 2200--- without supplements. Ditto for folate--- which has always been very high.

Any thoughts why one might have extremely high serum B12 but signs of B12 deficiency?

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