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SLC22A5 (Carnitine Transporter) & Carnitine Deficiency: Another Great Pretender?

Discussion in 'Genetic Testing and SNPs' started by jpredsoxdude00, Oct 24, 2017.

  1. jpredsoxdude00


    I have been doing research on this gene, as I suspect an underlying carnitine issue as a root of some of my issues. Currently, there is not much that I can find regarding which SNPs are relevant to carnitine deficiency, but I was hoping there may be someone who has more knowledge in this realm.

    This gene is associated with many conditions, including: hypoglycemia, Crohn's disease, lipid storage disease, arthritis, chronic fatigue, colitis, neuropathy, peripheral neuropathy, autonomic neuropathy, psoriasis, ulcerative colitis, etc. It seems a carnitine deficiency could certainly cause many problems outside of these defined diseases as well.

    Through searching on Promethease, Livewello, and Self Decode, I have a list of SNPs that I have mutations in, however very few of them have any data regarding the implications of these.

    Interestingly, my entire symptom set began occurring after infection with H. Pylori (blood test determined it was a "highly pathogenic" strain. Many of you are probably aware of Amy Yasko and her methylation research, and it seems that she has determined that H. Pylori may cause carnitine depletion, since it tends to raise Suberic Acid (a marker related to fatty acid oxidation). The link is here: I have found no research to back this up, but it seems she has clinical experience with this. If this is the case, and I had the SNPs in this gene, it seems that I could have had carnitine issues before that were unveiled by the H. Pylori infection, but once again, I have no idea what these SNPs mean.

    I have tried L-Carnitine Tartrate and Acetyl-L-Carnitine, with mixed results. L-Carnitine Tartrate had a slightly positive effect, if any, and the Acetyl caused a negative reaction. I rememeber what @Freddd has written about L-Carnitine Fumarate being the missing link, so to speak, with carnitine, so this will be my next attempt.

    Here are the SNPs I have identified that I carry (Minor= minor allele, often called "risk allele if the SNP is found to have a negative impact) :

    rs1045020 C/T; Minor: T
    rs17689550 C/T; Minor: T
    rs2073642 C/T; Minor: T
    rs2073643 C/T; Minor: C
    rs2631359 C/T; Minor: T
    rs274557 C/C; Minor: C
    rs274558 G/G; Minor: G
    rs274567 T/T; Minor: T
    rs274570 C/T; Minor: T
    rs274571 A/G; Minor: G
    rs4646301 A/G; Minor: A
    rs635619 A/G; Minor: A
    rs17622208 G/G; Minor: G
    rs2631372 C/G; Minor: C
    rs2631367 C/C; Minor: C
    rs13180186 G/T; Minor: T
    rs2631361 A/A; Minor: A
    rs2631362 A/G; Minor: G
    rs2631363 G/G; Minor: G
    There are a few others as well that I personally do not have mutations on.

    I have a feeling this gene could be a big problem for some people, and I want to spark a conversation to dig up what people know.
    PinkPanda and pattismith like this.
  2. alicec

    alicec Senior Member

    Here is the OMIM entry which lists the genetic variants known to be associated with primary carnitine deficiency.

    Here is a fairly recent paper which canvases some of the variants and has some useful references.

    Here is an older paper which suggests that some of the less serious variants might still have an effect on carnitine use and some drugs.

    This is one of the best places to find out what is really known about SNPs, as opposed to what many claim. Just type in the rs number you are interested in.

    I wouldn't place much credence in the claims of Amy Yasko. Frequently there is no research to back them or they are contrary to research. The so-called clinical experience may just be a good way of selling supplements.

    Here is an older thread on a related gene which may be of interest.
  3. jpredsoxdude00


    @alicec thanks for the information. I have seen the paper that discusses the 3 variants, however I can't translate that into the "rs number" to search if I carry those mutations. Do you know if they are SNPs or perhaps some other type of mutation?

    Also yes, I agree with you regarding Yasko. Anything she says I take with a grain of salt.
  4. PinkPanda

    PinkPanda Senior Member

    Very interesting!
    Sorry, I don't know much about the SNP's either.

    I also have some possible signs of carnitine deficiency. A while ago, I supplemented carnitine tartrate for a bit, didn't have the feeling it was massively helpful alone though.
    I could imagine that carnitine tartrate is better than acetyl-carnitine.

    L-Carnitine is the form found naturally in foods and I think carnitine tartrate comes closest to that. Acetyl-carnitine is already a 'finished product' produced by the body. I think I tolerate supplements that are found naturally in foods, and that the body usually ingests, better.

    A problem wih acetyl-carnitine could be, that the acetyl- is already bound. Carnitine can bind to fatty acids and transport them across the mitochondria membrane, but another function is binding acetyl-CoA:
    Acetyl-CoA+ Carnitine -> Acetyl-Carnitine + CoA-SH
    This lowers levels of Acetyl-CoA and increases free Coenzyme A/CoA-SH. Like that carnitine can activate the pyruvate dehydrogenase.
    Pruvate dehydrogenase is inhibited by high NADH, ATP or Acetyl-CoA. It also needs CoA-SH as cofactor. So by lowering acetyl-CoA and raising CoA-SH, carnitine can activate the pyruvate dehydrogenase. (Reference)

    So Acetyl-caritine might not be able to do that, because it already has acetyl- bound. If the carntine problem and some ME/CFS energy problems combine, then maybe carnitine tartrate could be better, because it also activates the pyruvate dehydrogenase?

    I checked for the SNP's you posted, I had:
    rs2073643 CC; Minor C
    rs2631367 CC; Minor C
    The other were all normal.

    I'm a bit confused on the issue, on one hand I don't think I have these very massive symptoms that many with primary carnitine deficiency have and I haven't been able to locate any SNP's (didn't go much into depth there htough, I think I ran a standard program that finds SNP's for some diseases and nothing came up. was a while ago..:D).
    On the other hand some of my symptoms are unusual, even for CFS. I have some cognitive issues, where I can concentrate ok, but have major problems doing some executive stiff, like orienting outside or driving a car. I thought maybe that might be a bit related to high ammonium and carnitine deficiency can cause hyperammonemia. I also had high unmetabolized fatty acids in a urine test.

    If you still have them available, could you maybe post the other SNP's for which you didn't have mutations?
    I read that 60 mutations in the SLC22A5 can cause primary carntine deficiency, but I haven't found which one's those are yet..
  5. jpredsoxdude00


    @PinkPanda interesting regarding pyruvate dehydrogenase. Perhaps this is why @Freddd 's suggestion of L-Carnitine Fumarate works better for most people. If I remember correctly, he mentioned that the L-Carnitine Fumarate is the specific fat transporter to the mitochondria.

    Its very interesting that you only had 2 mutations out of all of those. It makes me think I may have a very dysfunctional carnitine transporter. My symptoms have wavered, but I wouldn't call it CFS for myself as much as I would call it a set of bizarre neurological and muscular symptoms. It all started with H. Pylori for me, and then after eradication, I developed GI motility issues, mainly slow motility, which carnitine deficiency is linked to. Mitochondrial dysfunction as a whole can lead to autonomic nervous system dysfunction:

    The rs2631367 SNP is the one linked to Crohn's Disease, and the rs2073643 SNP is somewhat related to Asthma. These 2 SNPs are actually some of the only ones I could find data on. I am unsure of their specific relationship to systemic carnitine deficiency.

    Here is the primary source of SLC22A5 SNPs:
    Note that the for the ones I "don't have", some were because I simply am not positive for the SNP, but others were not genotyped by 23andme, meaning I could still have them, but they were not searched for when my genes were processed. You may find this to be the case for yourself as well.

    Regarding the 60 mutations in SLC22A5, I have not seen that before, but could very well make sense. Not sure about the number 60, though. The source for the SNPs doesn't list 60 of them. In general, it seems the case for many gene-based issues that many of the specific SNPs for a given enzyme have slight effects that, if by themselves, do not manifest into clinical symptoms. However, once these small defects begin to compile, together they can create a larger problem. It all depends on which SNPs are present. Some SNPs in other transporter genes, such as the serotonin transporter SLC6A4 that is the target of SSRI drugs, actually speed up the enzyme. Hence the reason why SSRI drugs can help some people; they block the action of the sped-up enzyme. So, its hard to assume the impact on any of these SNPs, especially when there is not much data on them. I would assume however, that at a certain point, if one were to have many SNPs for a certain gene, some sort of dysfunction is going to come out of that, even if some speed up the enzyme action and other slow it down.

    Aside from this gene, methylation issues can also cause carnitine deficiency, as methylation is required to synthesize it. I personally have many methylation SNPs that could be compiling the issue if my carnitine transporter is busted. Others many not have a carnitine transporter problem, but still have low levels of carnitine due to methylation defects.
    PinkPanda likes this.
  6. alicec

    alicec Senior Member

    Yes trying to track down rs numbers from descriptive titles can be painful. All three are SNPs c.1195C>T (p.R399W), c.1324_1325GC>AT (p.A442I), and c.43G>T (p.G15W) - taken in order

    a nucleotide change C>T at position 1195 results in a change from arginine (R) to tryptophan (W) at protein residue 399

    a dual nucleotide change GC > AT at position 1324-1325 leading to a change from alanine (A) to isoleucine (I) at protein residue 442 (well I think this would be given an rs number even though it is a dual nucleotide change, but maybe not)

    a nucleotide change G>T at position 43 leads to a change from glycine (G) to tryptophan (W) at protein residue 15.

    These are very rare SNPs and I wasn't necessarily thinking they might be relevant to you, it was more that this is a fairly recent paper and might have useful references for what is known.

    Here is the list of variants from NCBI which should give you reliable information of what is known about variants. They start with changes in the regulatory region in front of the gene (negative numbers) then run in order from the beginning to the end of the gene. Among other things you should be able to track down rs numbers from the position of the nucleotide change.

    What is the source?
  7. PinkPanda

    PinkPanda Senior Member

    Hello @jpredsoxdude00 ,
    Anything new with your carnitine supplements?

    I found this link with a number of defects in the carnitine transporter and then some show with an actual proven link like this one, but I wasn't able to find most SNPs in my 23andme results.

    Sorry, forgot to answer that

    Maybe there could also be an issue reminiscent of what Neil McGregor found while screening for unsual SNP's in ME/CFS, a high amount of mutations in G proteins etc.

    So you think this could also be an individual issue for you with the carnitine deficiency? Have you been able to have some gene tests on the issue? Or are you thinking that maybe a high number of SNPs without proven effect could be compiling into a problem? I guess that would be possible, like I said above, what Neil McGregor found with the many SNP's in certain genes, he seems to think that could imply that some of the function of G proteins etc could be impacted. He probably doesn't have any proven effect for all SNPs either.

    I also have a number of methylation mutations. It's really weird because I feel there is some carnitine issue for me and at the same time it interacts with CFS issues.. Don't know if defect methylation can be enough to create those carnitine issues.

    I have the feeling that there are some things interacting with methylcobalamin synthesis, but I don't really know what supplements would be helpful for that. I was thinking B5 or choline as they influence copper binding and methylation (more SAMe or copper might raise MTR/MTRR function) and then with what I wrote above, that carnitine can increase B5/CoA-SH . And your post got me thinking, that maybe carnitine could increase B5 and thereby copper binding/ MTR function. None of the supplements (choline, carnitine, B5) have worked really well yet. If something might reduce methylB12 synthesis that could also impact SAMe and carnitine production. I'm a bit unsure from which direction to try to fix the problem :)
    I have some MTHFR problems and had a lot of success with B2, so I thought maybe cofactors might be important.
    Last edited: Nov 10, 2017

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