nandixon
Senior Member
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I'm hoping people with 23andMe results will compare their results to mine below and post if they see a problem or not. Mine indicate a potential problem that might be applicable to others, and I think it would be good to know how prevalent this is in the ME/CFS community. Thanks!
As previously mentioned on the thread* for the DHFR SNPs, GTP cyclohydrolase I (GTPCH or GCH1) is the rate-limiting enzyme in the body's synthesis of tetrahydrobiopterin (BH4). [*http://forums.phoenixrising.me/index.php?threads/snps-for-dihydrofolate-reductase-dhfr.19563/]
BH4 is important in the production of neurotransmitters and also for regulation of the enzyme nitric oxide synthase (NOS). NOS 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.
Mutations in GCH1 can cause a deficiency of BH4, and so seems worth exploring to see if it may be compounding the problems some people also have in the methylation cycle genes, i.e., MTHFR, MTRR, CBS, etc.
I don't see where Amy Yasko has specifically addressed this gene in the work she's done primarily with autistic children, who appear to have similar methylation cycle problems. Perhaps it's not widely relevant there, or for us either, but every possibility we can at least eliminate brings us one step closer to finding a treatment for those who don't fully respond to a methylation protocol. Note that Yasko does place importance on BH4 via the MTHFR A1298C marker (rs1801131).
If Martin Pall, proponent of the nitric oxide/peroxynitrite theory for CFS/ME (and MCS, etc), was testing patients similarly to Yasko, I assume examination of the GCH1 gene would be at or near the top of his list. Note that this enzyme requires zinc as a cofactor.
I've given what I believe to be the normal (common) results for the alleles in parentheses. These SNPs are listed in the same order SNPedia gives here:
http://snpedia.com/index.php/GCH1
GCH1 SNPs:
rs10483639 +/+ CC (GG) (part of a 3 SNP haplotype w/ rs3783641 & rs8007267 associated w/ reduced levels of BH4; 2% frequency from openSNP)
rs104894433 thru -45 No Data
rs12147422 -/- TT (TT)
rs137852633 No Data
rs17738966 -/- GG (GG)
rs2878172 +/+ GG (AA) (17% frequency)
rs3783637 -/- CC (CC)
rs3783641 +/+ AA (TT) (part of haplotype w/ rs10483639 & rs8007267; "0%" frequency)
rs41298442 -/- TT (TT)
rs4411417 +/+ CC (TT) (higher tolerance to pain; 2% frequency)
rs7142517 -/- CC (CC)
rs752688 +/+ TT (CC) (2% frequency)
rs8007201 No Data
rs8007267 -/+ CT (CC) (part of haplotype w/ rs10483639 & rs3783641)
rs841 +/+ AA (GG) (associated w/ lower novelty seeking; 3% frequency)
rs998259 -/- CC (CC)
rs7147286 +/+ AA (GG) (not listed on SNPedia; 10% frequency)
GCH1 activity is regulated by GTP cyclohydrolase I feedback regulator (GCHFR). GCHFR stimulates GCH1 in the presence of L-phenylalanine. 23andMe gives one result for this gene, which I'm negative for:
rs2016546 -/- GG (GG)
As previously mentioned on the thread* for the DHFR SNPs, GTP cyclohydrolase I (GTPCH or GCH1) is the rate-limiting enzyme in the body's synthesis of tetrahydrobiopterin (BH4). [*http://forums.phoenixrising.me/index.php?threads/snps-for-dihydrofolate-reductase-dhfr.19563/]
BH4 is important in the production of neurotransmitters and also for regulation of the enzyme nitric oxide synthase (NOS). NOS 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.
Mutations in GCH1 can cause a deficiency of BH4, and so seems worth exploring to see if it may be compounding the problems some people also have in the methylation cycle genes, i.e., MTHFR, MTRR, CBS, etc.
I don't see where Amy Yasko has specifically addressed this gene in the work she's done primarily with autistic children, who appear to have similar methylation cycle problems. Perhaps it's not widely relevant there, or for us either, but every possibility we can at least eliminate brings us one step closer to finding a treatment for those who don't fully respond to a methylation protocol. Note that Yasko does place importance on BH4 via the MTHFR A1298C marker (rs1801131).
If Martin Pall, proponent of the nitric oxide/peroxynitrite theory for CFS/ME (and MCS, etc), was testing patients similarly to Yasko, I assume examination of the GCH1 gene would be at or near the top of his list. Note that this enzyme requires zinc as a cofactor.
I've given what I believe to be the normal (common) results for the alleles in parentheses. These SNPs are listed in the same order SNPedia gives here:
http://snpedia.com/index.php/GCH1
GCH1 SNPs:
rs10483639 +/+ CC (GG) (part of a 3 SNP haplotype w/ rs3783641 & rs8007267 associated w/ reduced levels of BH4; 2% frequency from openSNP)
rs104894433 thru -45 No Data
rs12147422 -/- TT (TT)
rs137852633 No Data
rs17738966 -/- GG (GG)
rs2878172 +/+ GG (AA) (17% frequency)
rs3783637 -/- CC (CC)
rs3783641 +/+ AA (TT) (part of haplotype w/ rs10483639 & rs8007267; "0%" frequency)
rs41298442 -/- TT (TT)
rs4411417 +/+ CC (TT) (higher tolerance to pain; 2% frequency)
rs7142517 -/- CC (CC)
rs752688 +/+ TT (CC) (2% frequency)
rs8007201 No Data
rs8007267 -/+ CT (CC) (part of haplotype w/ rs10483639 & rs3783641)
rs841 +/+ AA (GG) (associated w/ lower novelty seeking; 3% frequency)
rs998259 -/- CC (CC)
rs7147286 +/+ AA (GG) (not listed on SNPedia; 10% frequency)
GCH1 activity is regulated by GTP cyclohydrolase I feedback regulator (GCHFR). GCHFR stimulates GCH1 in the presence of L-phenylalanine. 23andMe gives one result for this gene, which I'm negative for:
rs2016546 -/- GG (GG)