Hi all. I'm new here. I'm looking into methylation now that Lyme+coinfect treatment hasn't given me the improvements I'd hoped. I had my SNPs tested with 23&Me on a friend's advice, and can see that there are possible issues that give me hope of further improvement with treatment.
I'd love some help with interpreting my SNPs from those further down this path than me. Brainfog is my number one problem, so it's taken me a while to compile this. I hope it includes everything and makes sense! Thanks in advance.
A little background:
1992 diagnosis: CFS/ME
2008 diagnosis: mitochondrial dysfunction / krebs cycle dysfunction; vascular endothelial dysfunction; fructose intolerance; leaky gut
2009 diagnosis: borrelia + babesia + bartonella + ehrlichia (i.e. Lyme & co-infections)
Have improved some since treating above, but still pretty much housebound.
Primary symptoms: brainfog (no 1!); depersonalisation; anxiety, or it's flipside - lethargy and apathy; mood swings; sleep problems - unrefreshing, wakeful ; poor short-term memory; poor short-term memory (sorry - couldn't resist! ;-) ); poor energy levels; reflux; high intraocular pressure & visual snow; sore feet & calves, & occasionally hands; hair loss on back of calves; plaque psoriasis & soft, creping skin, occasional smell of ammonia in sweat and sulphur in urine, also rarely ‘maple syrup’ smell in sweat (NB have not ingested MS – am on sugar free diet)
A lot of my symptoms come together - anxiety, wakefulness, sore feet & calves, sulphurous urine smell often ramp up together, and seem cyclical. I had assumed die-off of lyme or coinfection, but they don't seem to fit a rigid cycle, so wonder if there might be another explanation.
Common bloodwork results: usually low uric acid, occasionally low phosphate
______________________________________________________________________
So here are my Yasko SNPs, the 23&Me data is from the V4 chip. I have run the data through the following reports: Genetic Genie, Sterling's and Promethease. There are so many, I wasn't sure which to put. In the end I've picked out SNPs from Yasko's list regardless of result, and then added from Sterling's Methylation list where anything other than -/-. Where the Sterling's 'extra' is for the same gene as in Yasko's list - I've added in brackets in Yasko's list, otherwise the Sterling's 'extras' are in a separate list below.
COMT V158M -/-
COMT H62H -/-
COMT 61 (P199P) -/-
(Sterling's = COMT @rs6269 +/+)
VDR Taq Tt
VDR Fok Ff (Question over risk allele? "Risk Allele: T, 23andMe: A" Source: http://www.snpedia.com/index.php/Yasko_Methylation#VDR_Gene) (I'm AG)
(Sterling's = VDR Bsm +/-)
MAO A R297R +/+
ACAT 1-02 -/-
MTHFR C677T +/-
MTHFR 3 (P39P) -/-
MTHFR A1298C -/-
(Sterling's = MTHFR @rs3737964 & @rs4846048 both +/-)
MTR A2756G +/-
MTRR A66G +/-
MTRR K350A -/-
MTRR 11 (A664A) -/-
(Sterling's = MTRR @rs3776467 +/-)
BHMT 2 -/-
BHMT 8 +/-
(Sterling's = BHMT R239Q +/-)
AHCY 1 -/-
AHCY 19 -/-
CBS C699T +/+
CBS A360A -/-
(Sterling's = CBS A13637G & C19150T both +/+)
I realise that I miss out on some of Yasko's list due to 23&Me V4 chip – BHMT 1, BHMT 4, SHMT C1420T, SUOX S370S, NOS D298E etc.
The following are not in Yasko's list, but are in Sterling's Methylation list (where not -/-). I don't know which are relevant variants:
ACE Del16 +/+
ADD1 G460W +/-
DAO @rs3741775 +/-
FOLR2 +/-
GAD1 @ rs769407 +/-
GAD1 @ rs3791851 +/-
GAD1 @ rs12185692 +/-
GAD1 @ rs3791878 +/-
GAD1 @ rs10432420 +/-
GAD1 @ rs3828275 +/-
GAD1 @ rs701492 +/-
MTHFD1 G1958A +/-
MTHFD1L @rs17349743 +/-
MTHFD1L @rs803422 +/-
MTHFS +/+
NOS2 @rs2274894 +/-
NOS2 @rs2248814 +/-
NOS3 @rs3918188+/+
PEMT @rs4646406 +/+
SHMT2 @ rs34095989 +/+
TCN1 +/-
The following are my detox SNPs from Sterling’s (where not -/-) in case any are relevant to the methylation SNP interpretation.
CYP1B1 L432V +/-
CYP1B1 N453S +/-
CYP1B1 R48G +/-
CYP2C19*17 +/+
CYP2D6 S486T +/-
CYP2D6 T2850C +/-
GSTP I105V +/-
NAT2 A803G (K268R) +/-
NAT2 G590A (R197Q) +/-
NAT2 T341C (I114T) +/-
SOD2 +/-
SOD2 A16V +/-
PON1 Q192R +/-
Q1 - any comments on my SNPs and any explanations for my symptoms based on them would be most welcome!
Here is my (beginner's) simplistic interpretation based on looking at Yasko's Methylation Pathway diagram (and assuming the genes are expressed) : MTHFR, MTR, MTRR could be impacting normal function of the full cycle, BHMT could be impacting normal function of the shortcut, CBS could be 'draining the bath' (see also Q3 below). GST/SOD/GAD could be causing poor detox and/or excitotoxicity (I'm not sure if my SNPs are the relevant ones)? GAD?/MAO A/ACE could be causing neurotransmitter issues (again, not sure of relevancy of GAD1 SNP variants reported. Please see Q2)? Please confirm I'm on the right track / add to / pick apart!
______________________________________________________________________
Yasko’s Methylation Pathway diagram - there are some others on this that are not on her list. Some may be on Sterling's, but not obvious which variant. I realise I don't need to know all the SNPs on the diagram as you don't need to rectify some, but I think some of them will be useful to know (GAD, GST, SOD in particular from what I've read so far), and I'd be interested to know anyway. I'd like to put a tick next to the problematic genes on Yasko’s Methylation Pathway diagram to aid understanding, and I’m not sure which variants I should be looking for within the following:
OTC
NOS (NOS2/3? Either, both?)
GST (GSTM/P as found under detox? Either, both?)
SOD (SOD2/3 as found under detox? Either, both?)
DHPR
MAT
G6PDH
GAD (GAD1? 7 out of 11 GAD1 variants on Sterling's are +/-, the others are -/-)
SUOX
ACAT
SHMT
AHCY
Q2 - does anyone know the relevant variants for these & their rsID #s if on 23&Me V4 chip? Which of these, and those above Q1 that Yasko doesn't list, are relevant? I guess I'd like to produce a useful forum sig with my relevant SNPs.
______________________________________________________________________
I have found the following in Promethease that is not on Yasko’s MP diagram and is under Tongue Tie/Cleft Palate in Sterling’s:
CTH S4031l (rs1021737) +/+
It codes for cystathionine gamma-lyase (confusingly, the enzyme is also referred to as CGL and CSE) which breaks down cystathionine into cysteine and alpha-ketobutyrate, and possibly ammonia, and also breaks down cysteine into ammonia and hydrogen sulphide.
http://en.wikipedia.org/wiki/Cystathionine_gamma-lyase
Q3a - I realise I'm new at all this, but does anyone else think this should be under Methylation in Sterling’s? And appear in Yasko’s diagram (I'm sure not every SNP involved in methylation will be, but this seems important)? Cystathionine seems highly relevant to the pathway.
Q3b - if CBS SNPs are an upregulation, and this CTH SNP is a downregulation - isn't that going to produce a bottleneck between the two? Implications?
Q3c - can anyone confirm ammonia comes from cystathionine and not just cysteine?
Q3d - how does CTH affect the regular advice for CBS SNP management? Freddd suggests avoiding glutathione and it's precursors. I would think CTH would affect this advice?
______________________________________________________________________
Q4 - Are there any more relevant SNPs I should be looking for (outside of those discussed)?
______________________________________________________________________
Q5 - anything else?
Thanks again.
Nick
I'd love some help with interpreting my SNPs from those further down this path than me. Brainfog is my number one problem, so it's taken me a while to compile this. I hope it includes everything and makes sense! Thanks in advance.
A little background:
1992 diagnosis: CFS/ME
2008 diagnosis: mitochondrial dysfunction / krebs cycle dysfunction; vascular endothelial dysfunction; fructose intolerance; leaky gut
2009 diagnosis: borrelia + babesia + bartonella + ehrlichia (i.e. Lyme & co-infections)
Have improved some since treating above, but still pretty much housebound.
Primary symptoms: brainfog (no 1!); depersonalisation; anxiety, or it's flipside - lethargy and apathy; mood swings; sleep problems - unrefreshing, wakeful ; poor short-term memory; poor short-term memory (sorry - couldn't resist! ;-) ); poor energy levels; reflux; high intraocular pressure & visual snow; sore feet & calves, & occasionally hands; hair loss on back of calves; plaque psoriasis & soft, creping skin, occasional smell of ammonia in sweat and sulphur in urine, also rarely ‘maple syrup’ smell in sweat (NB have not ingested MS – am on sugar free diet)
A lot of my symptoms come together - anxiety, wakefulness, sore feet & calves, sulphurous urine smell often ramp up together, and seem cyclical. I had assumed die-off of lyme or coinfection, but they don't seem to fit a rigid cycle, so wonder if there might be another explanation.
Common bloodwork results: usually low uric acid, occasionally low phosphate
______________________________________________________________________
So here are my Yasko SNPs, the 23&Me data is from the V4 chip. I have run the data through the following reports: Genetic Genie, Sterling's and Promethease. There are so many, I wasn't sure which to put. In the end I've picked out SNPs from Yasko's list regardless of result, and then added from Sterling's Methylation list where anything other than -/-. Where the Sterling's 'extra' is for the same gene as in Yasko's list - I've added in brackets in Yasko's list, otherwise the Sterling's 'extras' are in a separate list below.
COMT V158M -/-
COMT H62H -/-
COMT 61 (P199P) -/-
(Sterling's = COMT @rs6269 +/+)
VDR Taq Tt
VDR Fok Ff (Question over risk allele? "Risk Allele: T, 23andMe: A" Source: http://www.snpedia.com/index.php/Yasko_Methylation#VDR_Gene) (I'm AG)
(Sterling's = VDR Bsm +/-)
MAO A R297R +/+
ACAT 1-02 -/-
MTHFR C677T +/-
MTHFR 3 (P39P) -/-
MTHFR A1298C -/-
(Sterling's = MTHFR @rs3737964 & @rs4846048 both +/-)
MTR A2756G +/-
MTRR A66G +/-
MTRR K350A -/-
MTRR 11 (A664A) -/-
(Sterling's = MTRR @rs3776467 +/-)
BHMT 2 -/-
BHMT 8 +/-
(Sterling's = BHMT R239Q +/-)
AHCY 1 -/-
AHCY 19 -/-
CBS C699T +/+
CBS A360A -/-
(Sterling's = CBS A13637G & C19150T both +/+)
I realise that I miss out on some of Yasko's list due to 23&Me V4 chip – BHMT 1, BHMT 4, SHMT C1420T, SUOX S370S, NOS D298E etc.
The following are not in Yasko's list, but are in Sterling's Methylation list (where not -/-). I don't know which are relevant variants:
ACE Del16 +/+
ADD1 G460W +/-
DAO @rs3741775 +/-
FOLR2 +/-
GAD1 @ rs769407 +/-
GAD1 @ rs3791851 +/-
GAD1 @ rs12185692 +/-
GAD1 @ rs3791878 +/-
GAD1 @ rs10432420 +/-
GAD1 @ rs3828275 +/-
GAD1 @ rs701492 +/-
MTHFD1 G1958A +/-
MTHFD1L @rs17349743 +/-
MTHFD1L @rs803422 +/-
MTHFS +/+
NOS2 @rs2274894 +/-
NOS2 @rs2248814 +/-
NOS3 @rs3918188+/+
PEMT @rs4646406 +/+
SHMT2 @ rs34095989 +/+
TCN1 +/-
The following are my detox SNPs from Sterling’s (where not -/-) in case any are relevant to the methylation SNP interpretation.
CYP1B1 L432V +/-
CYP1B1 N453S +/-
CYP1B1 R48G +/-
CYP2C19*17 +/+
CYP2D6 S486T +/-
CYP2D6 T2850C +/-
GSTP I105V +/-
NAT2 A803G (K268R) +/-
NAT2 G590A (R197Q) +/-
NAT2 T341C (I114T) +/-
SOD2 +/-
SOD2 A16V +/-
PON1 Q192R +/-
Q1 - any comments on my SNPs and any explanations for my symptoms based on them would be most welcome!
Here is my (beginner's) simplistic interpretation based on looking at Yasko's Methylation Pathway diagram (and assuming the genes are expressed) : MTHFR, MTR, MTRR could be impacting normal function of the full cycle, BHMT could be impacting normal function of the shortcut, CBS could be 'draining the bath' (see also Q3 below). GST/SOD/GAD could be causing poor detox and/or excitotoxicity (I'm not sure if my SNPs are the relevant ones)? GAD?/MAO A/ACE could be causing neurotransmitter issues (again, not sure of relevancy of GAD1 SNP variants reported. Please see Q2)? Please confirm I'm on the right track / add to / pick apart!
______________________________________________________________________
Yasko’s Methylation Pathway diagram - there are some others on this that are not on her list. Some may be on Sterling's, but not obvious which variant. I realise I don't need to know all the SNPs on the diagram as you don't need to rectify some, but I think some of them will be useful to know (GAD, GST, SOD in particular from what I've read so far), and I'd be interested to know anyway. I'd like to put a tick next to the problematic genes on Yasko’s Methylation Pathway diagram to aid understanding, and I’m not sure which variants I should be looking for within the following:
OTC
NOS (NOS2/3? Either, both?)
GST (GSTM/P as found under detox? Either, both?)
SOD (SOD2/3 as found under detox? Either, both?)
DHPR
MAT
G6PDH
GAD (GAD1? 7 out of 11 GAD1 variants on Sterling's are +/-, the others are -/-)
SUOX
ACAT
SHMT
AHCY
Q2 - does anyone know the relevant variants for these & their rsID #s if on 23&Me V4 chip? Which of these, and those above Q1 that Yasko doesn't list, are relevant? I guess I'd like to produce a useful forum sig with my relevant SNPs.
______________________________________________________________________
I have found the following in Promethease that is not on Yasko’s MP diagram and is under Tongue Tie/Cleft Palate in Sterling’s:
CTH S4031l (rs1021737) +/+
It codes for cystathionine gamma-lyase (confusingly, the enzyme is also referred to as CGL and CSE) which breaks down cystathionine into cysteine and alpha-ketobutyrate, and possibly ammonia, and also breaks down cysteine into ammonia and hydrogen sulphide.
http://en.wikipedia.org/wiki/Cystathionine_gamma-lyase
Q3a - I realise I'm new at all this, but does anyone else think this should be under Methylation in Sterling’s? And appear in Yasko’s diagram (I'm sure not every SNP involved in methylation will be, but this seems important)? Cystathionine seems highly relevant to the pathway.
Q3b - if CBS SNPs are an upregulation, and this CTH SNP is a downregulation - isn't that going to produce a bottleneck between the two? Implications?
Q3c - can anyone confirm ammonia comes from cystathionine and not just cysteine?
Q3d - how does CTH affect the regular advice for CBS SNP management? Freddd suggests avoiding glutathione and it's precursors. I would think CTH would affect this advice?
______________________________________________________________________
Q4 - Are there any more relevant SNPs I should be looking for (outside of those discussed)?
______________________________________________________________________
Q5 - anything else?
Thanks again.
Nick
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