When "Common SNPs" Matter

[Kathevans]

@ppodhajski Ok, in terms of MYRF rs174537, I’m GT , so it looks like a mixed bag with regard to my cholesterol. Interestingly, despite my high total numbers, my cardiac risk ratio always seems to be below 1.

There seems to be a link with ALA (though this may have to do with FAD genes I haven’t yet looked up). My NutrEval test last December showed a high need for this supplement, and suggested a dose of 200 mg/day. But I think I’ve read things on PR about putting off taking too much as it’s—possibly?—a chelator of mercury, or in any case very activating other than in small doses throughout the day.

Are there other approaches/cofactors that could help this snp/my cholesterol?

I’m still working on the PEMT snps you’ve provided a link to, though I, like you, am BHMT rs3733890 AG (I think you meant heterozygous, right?). It so happens, I eat eggs pretty much every day, and I’ve been increasing my zinc intake via BodyBio liquid drops from nil to about 20 mg/day over the last couple of months. So, perhaps I’m doing what I can for the moment for my PEMT.

As to your suggestion for @ahmo’s sulphur sensitivities (I love your new Avatar! Almost Ents!), I was curious because I eat a lot of sulphur, not just in eggs, but also veggies—ie cabbage and onions—and thought I did ok on them. I have SUOX rs10876864 AG, as do you, and would probably also benefit from supplementary molybdenum, though I tested in the ‘normal’ range for it. My eyes do sting a lot and are watery, though I thought that might be either oxalates, which I understand can collect in the eyes and I’m still dumping, or low B2, which I take very little of at this point because it definitely seems to drive my need for folate (and I am less than a month into methylation with MeB12 and folate at low doses: 250mcg and 100mcg) (I take higher B6 for the oxalates, though I know I ought to take more B2 as well...)

@Sea Yes, thank-you. I had to read it over a couple of times—but it does help. I’m still thinking about your definition of complementary vs synonymous vs missense. But I’ll try to read up on it!

Searching for my inner-scientist...

Now back to Dr. Zeisel.

 

[Violeta]

I have 3x homozygous PEMT. One is 7.1% frequency, 17.7, 22.1% I've found citicoline + lecithin very helpful.

@ahmo, have you tried choline bitartrate? I am looking for a comparison between the citicholine and choline bitartrate.

 

[ahmo]

@ppodhhajski May it be so. Increasing my molybd in the moment.

@Violeta Yes, I used choline bitartrate for a couple years. Until I found articles linking it to heart issues. that's when I switched to the expensive Bio Pur phos.choline, for about a year, until that became financially impossible. That's when I began the citicholine, earlier this year. I considered Alpha (?) coline, but chose the citicholine instead, haven't tried the other. There's a bit of info on this thread I started about types of choline.

 

[Tammy]

All cells require inorganic sulfate for normal function. Sulfate is among the most important macronutrients in cells and is the fourth most abundant anion in human plasma (300 μM). Sulfate is the major sulfur source in many organisms, and because it is a hydrophilic anion that cannot passively cross the lipid bilayer of cell membranes, all cells require a mechanism for sulfate influx and efflux to ensure an optimal supply of sulfate in the body. The class of proteins involved in moving sulfate into or out of cells is called sulfate transporters.

This sparked a memory so I went and found some notes I had taken.......almost 12 years ago! I was trying to figure out what I needed to do based on some lab reports I had gotten back (unfortunately don't have the results anymore).......... I found the notes though.......and this is some of what I wrote ............"I have low sulfate levels but why?? Possible reasons.......High cytokine levels? Sulfate reducing bacteria? Sulfite sensitivity? Sulphation crucial for integrity of mucous membranes. Things that may help......methionine, Molybdenum, taurine." In bold letters my notes said I NEED INORGANIC SULFATE...........but at the time I was having a hard time figuring out if I needed actual sources of inorganic sulfate and what are those sources or if the methionine, molybdenum and taurine is what I needed to take. You mentioned sulfate transporters.............what are they........... how do we help these transporters?[/QUOTE]

 

[Violeta]

@ppodhhajski May it be so. Increasing my molybd in the moment.

@Violeta Yes, I used choline bitartrate for a couple years. Until I found articles linking it to heart issues. that's when I switched to the expensive Bio Pur phos.choline, for about a year, until that became financially impossible. That's when I began the citicholine, earlier this year. I considered Alpha (?) coline, but chose the citicholine instead, haven't tried the other. There's a bit of info on this thread I started about types of choline.

Oh no, choline bitartrate and heart issues, I'll have to look that up.

So you found a good source of economical citicholine? I'll have to look that up, too.

Thank you!

 

[ahmo]

@Violeta, yes, I started w/ Healthy Origins, then switched to powder from an ebay seller.

 

[Valentijn]

Ok, in terms of MYRF rs174537, I’m GT , so it looks like a mixed bag with regard to my cholesterol. Interestingly, despite my high total numbers, my cardiac risk ratio always seems to be below 1.

I'm not sold on that SNP being significantly related to cholesterol. One study from the US claims that it is, but another study from Italy (inCHIANTI) reviewed in that US study shows no statistical significance. It also shows that the difference between the apparent "best" genotype for rs174537 in the context of cholesterol (GG) and the heterozygous getontype (GT) is tiny ... 118.0 versus 118.3, respectively. Similarly, for total cholesterol the heterozygous genotype is slightly lower than the GG genotype: 194.2 versus 194.4. So from a cholesterol perspective, GT is just as good as GG.

It's also worth noting that the cholesterol values in the study are on the high end of the healthy range, or a bit beyond it. Nowhere near the level where they could potentially be low enough to cause a different set of problems. So it looks like lower cholesterol is better, at least as far as the impact of this SNP is concerned.

And the cholesterol results in this study, while seeming to having a decent p-value for a SNP study, are probably highly impacted by the researchers opting to exclude extreme values. Lack of that exclusion in the inCHIANTI study is probably why cholesterol results did not achieve statistical significance, and it is highly suspicious that the US research team did exclude it.

At the very very least, both sets of data should be presented, with and without the exclusions, such as in a scatter plot where each value would appear on a diagram. As it is, we don't know if the data was somewhat selectively excluded for the express purpose of making their findings appear stronger.

Something else to consider, based on that same study and mentioned in the discussion, is that diet is also a very big factor. In fact, Table 2 suggests it is a much bigger factor than rs174537. As an example, the difference between total cholesterol levels for GG versus the TT subjects in either study is about 8. Whereas the difference between subjects with any genotype from Italy versus subjects with the same genotype from the US is about 15.

 

[Kathevans]

@Valentijn Thanks for this… Unfortunately, I look at total cholesterol levels in this study and find no reassurance. Mine are higher! Although I guess this is just about the association, or relationship between fatty acids and plasma levels. So, knowing that at bottom, very little cholesterol comes from the food we eat—I think I’ve heard around 15%--I’m left wondering, why my high numbers? I’ve also read that cholesterol, or fat in general, is one way our bodies get rid of toxins. Yikes, that makes me wonder if I’m full of all sorts of bugs—when of course, with my gut there is every reason to suppose I am.

I did have a look at ‘Table 2” and do see the difference between those of us in the US and folks in bella Italia. The Italians have higher overall cholesterol, but also higher Triglycerides, the good stuff. Maybe that 15 point difference is the Mediterranean diet dividend!

 

[Gondwanaland]

Triglycerides, the good stuff.

Triglycerids is bad stuff. It comes from carbs.

very little cholesterol comes from the food we eat

Some foods DO raise your cholesterol, like full fat dairy, and greasy meats, and lard, and tallow. Eggs and avocado have been absolved.

 

[Kathevans]

Oh woops! I guess I meant HDL, then, right?

 

[Valentijn]

So, knowing that at bottom, very little cholesterol comes from the food we eat—I think I’ve heard around 15%--I’m left wondering, why my high numbers?

Genetic factors can play a huge part in cholesterol levels. So there might be somewhere else that you have a high-cholesterol variant which is having a bigger impact than your lower-cholesterol variant for rs174537.

 

[calexis6666]

I don't understand why I react to epsom salt baths when my body so needs the sulfate. I read those with hydrogen sulfide SIBO may not do well with the baths. How else will I get the sulfate into my body?