The power and pitfalls of omics part 2: epigenomics, transcriptomics and ME/CFS
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Genetic Variation in Glutathione-Related Genes and Body Burden of Methylmercury

Discussion in 'Other Health News and Research' started by Waverunner, Aug 27, 2011.

  1. Waverunner

    Waverunner Senior Member

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    Can anyone translate this into 23andme results? The full study can be found under the following link.

    http://www.scribd.com/doc/6430904/G...elated-Genes-and-Body-Burden-of-Methylmercury

    BACKGROUND:Exposure to toxic methylmercury (MeHg) through ?sh consumption is a large prob- lem worldwide, and it has led to governmental recommendations of reduced ?sh consumption and blacklisting of mercury-contaminated ?sh. The elimination kinetics of MeHg varies greatly among individuals. Knowledge about the reasons for such variation is of importance for improving the risk assessment for MeHg. One possible explanation is hereditary differences in MeHg metabolism. MeHg is eliminated from the body as a glutathione (GSH) conjugate. OBJECTIVES:We conducted this study to assess the in?uence of polymorphisms in GSH-synthesizing [glutamyl-cysteine ligase modi?er subunit (GCLM-588) and glutamyl-cysteine ligase catalytic subunit (GCLC-129)] or GSH-conjugating [glutathioneS-transferase pi 1 (GSTP1-105 andGSTP1-114)] genes on MeHg retention. METHODS:Based on information obtained from questionnaires, 292 subjects from northern Sweden had a high consumption of ?sh (lean/fat ?sh two to three times per week or more). We measured total Hg in erythrocytes (Ery-Hg) and long-chain n-3 polyunsaturated fatty acids in plasma (P-PUFA; an exposure marker for ?sh intake). RESULTS:TheGSTP1 genotype modi?ed Ery-Hg; effects were seen forGSTP1-105 and -114 sepa- rately, and combining them resulted in stronger effects. We found evidence of effect modi?cation: individuals with zero or one variant allele demonstrated a steeper regression slope for Ery-Hg (p = 0.038) compared with individuals with two or more variant alleles. TheGCLM-588 genotype also in?uenced Ery-Hg (p = 0.035): Individuals with theGCLM-588 TT genotype demonstrated the highest Ery-Hg, but we saw no evidence of effect modi?cation with increasing P-PUFA. CONCLUSIONS:These results suggest a role of GSH-related polymorphisms in MeHg metabolism.
     
  2. richvank

    richvank Senior Member

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    Hi, Waverunner.

    I'm glad you are tracking down information on the glutathione-related SNPs. I think that SNPs involved with the glutathione system may be major keys toward understanding why some people get ME/CFS, while the vast majority of the population does not. I suspect that people whose bodies are not able to make, recycle, or use glutathione as well as those of the majority will be more vulnerable to developing ME/CFS. If the GD-MCB hypothesis is valid, I think this has to be true.

    The three polymorphisms that were found to have effects in this study are all included in the 23andme genotype panel.

    Here are my results for them:

    rs41303970: GG

    rs1695: AA

    rs1138272: CC

    It appears that 23andme is considering the complementary DNA strand from the one used in this study.

    Because I am homozygous on all three of them, because the frequency of being homozygous for the variant that causes effects on mercury in erythrocytes in each case is small, and because I'm not aware of any problem with methylmercury detox in myself (note that I don't have CFS/ME myself), I'm guessing that my values represent the norm values for these SNPs. I know this to be true of the first one, because G is complementary to C.

    I know that the latter two SNPs (those involving GSTP1) do occur in many PWMEs, because they are included on the Genovations Detoxigenomic Profile, and I have received results from this profile from quite a few PWMEs over the past few years. Also, Dr. John McLaren Howard of AcumenLab in the UK measures RBC glutathione transferase activity (which is GSTP1 activity) and finds it to be low in quite a few PWMEs, also. So I think all of this is consistent, and I think it does mean that these SNPs can be important contributors to ME/CFS onset in some people.

    Best regards,

    Rich
     
  3. Waverunner

    Waverunner Senior Member

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    Hi Rich,

    thanks a lot for your answer. I didn't know where to put this study and I didn't want to flood the Methylation forum with SNP studies but next time I put it there if it has to do with Glutathione. Maybe someone can move it there. My results are:

    rs41303970: GG

    rs1695: AG

    rs1138272: CC

    I can add a little bit more information on rs1695 from SNPedia but only regarding asthma and unfortunately not on AG, which I have:

    Genotype Effect
    rs1695(A;A) normal asthma risk in certain populations
    rs1695(A;G) ?
    rs1695(G;G) 3.5x asthma risk in certain populations
     
  4. richvank

    richvank Senior Member

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    Hi, Waverunner.

    Thanks for the information. If you don't mind saying, do you have asthma?

    Rich
     
  5. Waverunner

    Waverunner Senior Member

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    Yes, I do. Sometimes more, sometimes less.
     
  6. sandralee

    sandralee

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    Sydney, Australia
    Hi Waverunner and Rich,

    I have exactly the same SNPs as you, Waverunner, but I don't have asthma.

    Sandra
     
  7. Waverunner

    Waverunner Senior Member

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    Hi Sanrda,

    thanks for your answer. I bet environment and other SNPs play an important role as well. Hopefully the near future will tell us more about it.
     

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