nandixon
Senior Member
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Here are the SNPs that 23andMe gives for dihydrofolate reductase (DHFR). Currently there are twelve of them. This enzyme performs the first two steps in the 4-step transformation of the synthetic form of folate, i.e., folic acid, into biologically active "L-methylfolate" (and folinic acid).
Since hopefully most people are avoiding folic acid to the extent they can, a more important role for DHFR is in regeneration of tetrahydrobiopterin (BH4) from BH2.
BH4 is important in the production of neurotransmitters and also for regulation of the enzyme nitric oxide synthase (NOS), which can potentially become dysregulated ("uncoupled") when BH4 is deficient and produce too much nitric oxide and superoxide, leading to peroxynitrite and, theoretically, exacerbating the chronically high levels of oxidative stress that are seen in CFS/ME.
(The rate-limiting step for production of BH4 itself is GTP cyclohydrolase I, aka GTPCH or GCH1 on 23andMe. I'll be making another thread for GCH1. Mutations in GCH1 can cause a deficiency of BH4, and I think it's worth exploring to see if it may be compounding the problems we seem to have in the methylation cycle genes, i.e., MTHFR, MTRR, CBS, etc.)
Rich had at one point been interested in what CFS/ME peoples' results might be for DHFR and posted his 23andMe results on another thread. Assuming I've analyzed things correctly, his results appear to be completely normal (homozygous -/- throughout). Mine are identical to his with only one exception: the SNP rs1650697 (aka C35T or G-437A) that overlaps with a coding region for the gene MSH3 is homozygous (+/+) for the variant alleles (AA). I'm not sure whether this single homozygous result by itself is significant, but when paired with another SNP (rs1105525 aka G308A) which 23andMe unfortunately doesn't test for, it can act as a major promoter of DHFR, increasing its production/activity. In theory that actually might be helpful for regenerating BH4. (But it might be bad with respect to cancer growth. Green tea, for example, is an inhibitor of DHFR, thus its anti-cancer benefits.)
Below are my results for people to compare to theirs. Again, I doubt the one positive SNP is relevant/detrimental for CFS/ME, but other people might have different results for the other SNPs. (I think GCH1 is generally going to be much more problematic.)
DHFR SNPs:
rs7387 A or T TT (-/-)
rs1643659 C or T TT (-/-)
rs1677693 G or T GG (-/-)
rs1643649 C or T TT (-/-)
rs11951910 C or T TT (-/-)
rs865646 G or T GG (-/-)
rs13161245 A or G AA (-/-)
rs10072026 C or T TT (-/-)
rs11490741 C or T CC (-/-)
rs863215 C or T CC (-/-)
rs1478834 A or C CC (-/-)
DHFR, MSH3 rs1650697 A or G AA (+/+; 4% frequency)
Since hopefully most people are avoiding folic acid to the extent they can, a more important role for DHFR is in regeneration of tetrahydrobiopterin (BH4) from BH2.
BH4 is important in the production of neurotransmitters and also for regulation of the enzyme nitric oxide synthase (NOS), which can potentially become dysregulated ("uncoupled") when BH4 is deficient and produce too much nitric oxide and superoxide, leading to peroxynitrite and, theoretically, exacerbating the chronically high levels of oxidative stress that are seen in CFS/ME.
(The rate-limiting step for production of BH4 itself is GTP cyclohydrolase I, aka GTPCH or GCH1 on 23andMe. I'll be making another thread for GCH1. Mutations in GCH1 can cause a deficiency of BH4, and I think it's worth exploring to see if it may be compounding the problems we seem to have in the methylation cycle genes, i.e., MTHFR, MTRR, CBS, etc.)
Rich had at one point been interested in what CFS/ME peoples' results might be for DHFR and posted his 23andMe results on another thread. Assuming I've analyzed things correctly, his results appear to be completely normal (homozygous -/- throughout). Mine are identical to his with only one exception: the SNP rs1650697 (aka C35T or G-437A) that overlaps with a coding region for the gene MSH3 is homozygous (+/+) for the variant alleles (AA). I'm not sure whether this single homozygous result by itself is significant, but when paired with another SNP (rs1105525 aka G308A) which 23andMe unfortunately doesn't test for, it can act as a major promoter of DHFR, increasing its production/activity. In theory that actually might be helpful for regenerating BH4. (But it might be bad with respect to cancer growth. Green tea, for example, is an inhibitor of DHFR, thus its anti-cancer benefits.)
Below are my results for people to compare to theirs. Again, I doubt the one positive SNP is relevant/detrimental for CFS/ME, but other people might have different results for the other SNPs. (I think GCH1 is generally going to be much more problematic.)
DHFR SNPs:
rs7387 A or T TT (-/-)
rs1643659 C or T TT (-/-)
rs1677693 G or T GG (-/-)
rs1643649 C or T TT (-/-)
rs11951910 C or T TT (-/-)
rs865646 G or T GG (-/-)
rs13161245 A or G AA (-/-)
rs10072026 C or T TT (-/-)
rs11490741 C or T CC (-/-)
rs863215 C or T CC (-/-)
rs1478834 A or C CC (-/-)
DHFR, MSH3 rs1650697 A or G AA (+/+; 4% frequency)