FUT2 genetics

[kraken]

Hey guys, was wondering if anybody else got some opinions on FUT2 genetics. Here's an article about it: http://metabolichealing.com/fut2-gene-mutations-your-gut-flora/, there's some on pubmed as well. My genetics results show:

FUT2rs492602 G GG+/+
FUT2rs601338 A AA+/+
FUT2rs602662 A AA+/+

This means that i'm a non-secretor thus having problem with keeping a balanced flora.

I'm beginning to think more and more that those genetics could be a strong indication of my present and past gut health. I've suspected Candida problems for a time and started a protocol about 2 weeks ago including Berberine, Oregano oil, Molybednum and NAC. I seem to do pretty well as I've experienced a lot of relief from my symptoms already (a long list). Experiencing some die-off though and crap like 3+ times a day.

Now I'm thinking about adding these probiotics (mainly Bifidobacterium strain which is belived to be extra good for FUT2 non-secretors): http://www.iherb.com/Renew-Life-Ultimate-Flora-RTS-Colon-Care-Probiotic-15-Billion-30-Veggie-Caps/54406#p=1&oos=1&disc=0&lc=en-US&w=ultimate flora 15 billion&rc=167&sr=null&ic=5

 

[Valentijn]

FUT2rs492602 G GG+/+
FUT2rs601338 A AA+/+
FUT2rs602662 A AA+/+

This means that i'm a non-secretor thus having problem with keeping a balanced flora.

Why do you think that those SNPs mean that you have a major problem with FUT2?

 

[Mogwai]

Why do you think that those SNPs mean that you have a major problem with FUT2?

The MTHFRSupport Variant Report? That's what I'm betting on.

Mine shows the same thing.

Do you have other thoughts, Valentijn?

I also have elevated serum concentrations of Vitamin B-12, and low/zero(!) levels of bifidobacterium according to my CDSA. Not uncommon amongst us lot!

I've been working on my gut, unsuccessfully, for a while now...

@kraken - let me know how you get on with that probiotic. Thanks.

 

[Valentijn]

@Mogwai -

It does look like they have an impact, but the research says that they're all basically inherited as a cluster, hence someone will typically have the +/+ for all three, or +/- for all three, or -/- for all three. Hence it's no more meaningful to be +/+ for all three than it would be to be +/+ for just one.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2673801/ basically says that they found that rs492602 and rs601338 were equivalent ("in perfect LD") and that rs602662 was extremely similar ("in strong linkage disequilibrium". And they attribute any problems associated with the three SNPS to the stop-gain nonsense mutation of rs601338 resulting in early termination of the FUT2 enzyme.

The "A" allele results in the early termination, and is associated with lower B12 serum levels. When homozygous for "AA" it also confers complete protection from Noroviruses as described at http://www.omim.org/entry/182100#0001 , which is probably why it is such a common mutation. In the general population, the frequency of the "A" allele is 32.4%, which goes up to 50% or higher in Europeans and Africans. Asians very rarely have the "A" allele. So basically the allele is common as dirt, with 10.5% of the general population calculated as being homozygous, and 43.8% being heterozygous. In European populations, up to 30% are actually homozygous and up to 50% heterozygous.

Regarding B12 levels, the effects are somewhat small. Having the AA or AG genotype accounts for a 2.5-3.5% reduction in serum B12 levels, with no significant difference from being homozygous versus heterozygous.

So about 44% of people in the general population have a small reduction in serum B12 due to the mutation, and 75%+ of Europeans. The reason complete lack of FUT2 gene functionality isn't a problem is because it's redundant. FUT1 creates the same functional enzyme as FUT2, Galactoside 2-alpha-L-fucosyltransferase. It's not very clear what the mechanism is for how FUT1 and FUT2 impact on B12 levels, but B12 absorption problems (versus low intake) are mentioned, so maybe injections are more effective in treating low B12 levels than oral supplementation.

 

[Mogwai]

@Valentijn Thorough as ever. Thank you.

 

[jepps]

@Mogwai -

The reason complete lack of FUT2 gene functionality isn't a problem is because it's redundant. FUT1 creates the same functional enzyme as FUT2, Galactoside 2-alpha-L-fucosyltransferase. It's not very clear what the mechanism is for how FUT1 and FUT2 impact on B12 levels, but B12 absorption problems (versus low intake) are mentioned, so maybe injections are more effective in treating low B12 levels than oral supplementation.

http://www.ncbi.nlm.nih.gov/pubmed/24733310

All three methods showed distinct clustering of the intestinal microbiota and significant differences in abundances of several taxa representing dominant microbiota between the non-secretors and the secretors as well as between the FUT2 genotypes. In addition, the non-secretors had lower species richness than the secretors

The study says, that we need more probiotic nutrition and Supplementation with FUT2-mutation.

Valentin, did you only refer to B12 concerning FUT2, or did you mean, that refering probiotic diversity FUT2-mutation is also redundant?

Regards, jepps

 

[Valentijn]

The study says, that we need more probiotic nutrition and Supplementation with FUT2-mutation.

The study doesn't say that at all: they don't use the word "supplement" even once, and "probiotics" are mentioned only to specify that study participants did not take them for at least a week before the trial.

While it is possible that those things might potentially help a bit, the study is only saying that FUT2 status is causing a different fecal microbe profile. The more likely scenario is that FUT2 itself is forcing this profile to be different, hence it might actually indicate that probiotics and/or other measures are doomed to failure because of the FUT2 issues.

Valentin, did you only refer to B12 concerning FUT2, or did you mean, that refering probiotic diversity FUT2-mutation is also redundant?

I was referring only to B12 and FUT2 in the prior post, not anything regarding bacteria.

 

[jepps]

The more likely scenario is that FUT2 itself is forcing this profile to be different, hence it might actually indicate that probiotics and/or other measures are doomed to failure because of the FUT2 issues.

I was referring only to B12 and FUT2 in the prior post, not anything regarding bacteria.

Thank you very much, Valentijn, I understand, and this is not a good thing.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098274/

Moreover, bifidobacterial diversity (p<0.0001), richness (p<0.0003), and abundance (p<0.05) were significantly reduced in the samples from the non-secretor individuals as compared with those from the secretor individuals.

Maybe supplementing bifido, resistant starch and prebiotic help.

Ripley (thanks Ripley) postet an interesting link, that says, that bladderwrack has high contents of fucose that promotes fucolation. Maybe this helps in addition to resistant starch and prebiotics for promoting FUT2-mutation.

http://n-equals-one.com/blogs/2010/10/13/gene-copy-numbers-autism-and-seaweed/

In general, fucoidans are a family of high molecular weight sulfated polysaccharides, widely dispersed in the cell walls of brown seaweed. The fucoidan found in bladderwrack has been reported to reduce inflammatory brain damage and rats given fucoidan treatment after collagenase-induced intracerebral hemorrhage had reduced
inflammation in the vicinity of the hematoma after three days while also showing significantly more rapid improvement of motor function in the first week following hemorrhage and better memory retention.

Regards jepps

 

[jepps]

But, Valentijn, do you know this: 23andme shows a long list of FUT2 genes, for 1/3 I have the ancestry allele, for 2/3 I have the risk allele. Does this mean, that FUT2 works for 1/3?

And means homozygot 0% activity?

 

[Valentijn]

But, Valentijn, do you know this: 23andme shows a long list of FUT2 genes, for 1/3 I have the ancestry allele, for 2/3 I have the risk allele. Does this mean, that FUT2 works for 1/3?

How are you determining that the alleles you have are related to a risk? Usually the only way to do that is by reading the research which has been done regarding those SNPs.

And means homozygot 0% activity?

No, even being homozygous for the mutation which prematurely terminates FUT2 from creating its protein won't mean 0% enzyme activity, because FUT1 makes exactly the same protein.

 

[jepps]

How are you determining that the alleles you have are related to a risk? Usually the only way to do that is by reading the research which has been done regarding those SNPs..

I assume, that this is the right side for researches:

http://www.snpedia.com/index.php/Rs601338


No, even being homozygous for the mutation which prematurely terminates FUT2 from creating its protein won't mean 0% enzyme activity, because FUT1 makes exactly the same protein.[/quote]

Thank you very much again. So we´ve more ways for enzyme activity. Unless it´s no fault to supplement higher with probiotics and prebiotics, as this link suggests:

http://gut.bmj.com/content/62/5/787.long#ref-54

“Polymorphisms in IBD-related genes that regulate mucus glycosylation, such as Fut2, which encodes α1,2-fucosyltransferase and is associated with abnormal bacterial profiles, may selectively improve response to alternative bacterial nutritional sources, such as prebiotics.54”

Best regards, jepps

 

[Valentijn]

Thank you very much again. So we´ve more ways for enzyme activity. Unless it´s no fault to supplement higher with probiotics and prebiotics, as this link suggests:

Actually they seem to be suggesting that only some genotypes would respond to antibiotics, thought the sentence structure is rather convoluted. They aren't at all saying that it will compensate for FUT2 problems, and the paper isn't about FUT2 at all but just mentioning it peripherally as another potential source of problems.

 

[Valentijn]

I took a quick look at the frequency of rare and missense/stop-gain mutations in the 23andMe data of 23 ME patients and 23 somewhat matched controls. Red SNPs are missense mutations, and purple in known pathogenic. Yellow boxes indicate a genotype which is prevalent in 5-10% of the general population, and orange indicates 2.5-5% prevalence. Green is used for anything with greater than 10% prevalence, yet might be of interest due to increased prevalence in patients and/or being missense mutations.

So we do have more rare genotypes and missense mutations in FUT2, including for the SNP which prematurely terminates the gene's protein. But allele prevalence in European populations is very high, around 50-60%, so we're looking pretty normal at 57%, though the controls are a little lower at 43%, so that might be a little interesting.

Also a few more rare genotypes in FUT1 for ME patients than controls, but again very normal when compared to expected prevalence rates. And the controls have several missense mutations which the ME patients are lacking.

 

[jepps]

I have FUT2:
rs601338 AA
rs1800027 CC
rs602662 AA

FUT1:
rs12611028 CC
rs16982283 CC
rs4015 CC
rs2071699 GG

There´s a research for the following snp´s according to Crohn´s disease:
FUT2:
rs1047781 risk T
rs281377 risk T

http://www.ncbi.nlm.nih.gov/pubmed/24720527