My results from Sciona/Cellf

[MeSci]

Finally done some analysis on my results from 2007(!) with the help of the Nutrametrix document I posted a link to recently. Hope I've got it right - haven't done any of my usual double- and treble-checking due to lack of time and energy. Please feel free to comment on or query anything.

(Anti)oxidant/detox/inflammation

GSTM1 deleted: compromised Phase II detoxification and antioxidant activity.

GSTP1 A313G and C341T: reduced AO/detox activity.

GSTT1 (DEL): gene present, so no adverse effect on Phase II detoxification activity or antioxidant activity

IL-6 G(-174)C but not G(-634)C: increased inflammation but less than if both variations present

MnSOD C(-28)T: variation absent, so enzyme is concentrated in mitochondria which may not be benefical. Advice: increase AO consumption.

SOD3 C760G: variation absent; activity should be normal

TNF-α G(-308)A: poss. excess inflammation due to increased levels/activity

BMI

PPARγ2 Pro12Ala: associated with lower BMI

Bone

COL1A1 GspIT/+2046 G>T: variation absent so no reduction in bone strength

IL-6 G(-174)C but not G(-634)C: What are implications?

TNF-α G(-308)A: What are implications?

VDR Bsml/Variation +58980 A>G: reduced calcium absorption due to reduced Vitamin D response

VDR Fok1; Variation +25920 T>C: reduced calcium absorption due to reduced Vitamin D response

VDR Taql/ Variation +60058 T>C: reduced calcium absorption due to reduced Vitamin D response

Heart/vascular

ACE insertion/deletion: bp increase; alterations in levels of total cholesterol and plasma triglycerides. Advice: exercise, reduce carbs, correct BMI.

APOC3 C3175G: variation absent so no adverse effect on APOC3, cholesterol, plasma triglycerides or VLDL-triglycerides

CBS C699T: may reduce homocysteine.

CETP G279A: variation absent so no adverse effect on plasma CETP levels, HDL levels or risk of cardiovascular disease

eNOS G894T: less nitric oxide, so less smooth muscle relaxation; reduced platelet activity. Advice: increase omega-3 intake.

IL-6 G(-174)C but not G(-634)C: What are implications?

LPL C1595G: no variation. Normal allele has been associated with higher levels of VLDL and triglycerides and lower levels of HDL

MnSOD C(-28)T: variation absent: What are implications?

MTHFR C677T but not A1298C: increased homocysteine levels but presumably not as much as if both variations present

MS_MTRR A66G: variation absent; normal allele associated with slight increase in homocysteine levels

ACE insertion/deletion: bp increase; alterations in levels of total cholesterol and plasma triglycerides. Advice: exercise, reduce carbs, correct BMI.

APOC3 C3175G: variation absent so no adverse effect on APOC3, cholesterol, plasma triglycerides or VLDL-triglycerides

CBS C699T: may reduce homocysteine.

MTR A2756G: variation – which I don't have - may lead to lower homocysteine levels

PPARγ2 Pro12Ala: associated with higher HDL levels

SOD3 C760G: variation absent; activity should be normal

TNF-α G(-308)A: What are implications?

Insulin sensitivity

ACE insertion/deletion: reduction in insulin sensitivity. Advice: exercise, reduce carbs, correct BMI.

IL-6 G(-174)C but not G(-634)C: reduced insulin sensitivity?

PPARγ2 Pro12Ala: associated with improved insulin sensitivity

TNF-α G(-308)A: Presumably reduced sensitivity

VDR Bsml/Variation +58980 A>G: Presumably reduced sensitivity

VDR Taql/ Variation +60058 T>C: Presumably reduced sensitivity

 

[MeSci]

I now have the rs numbers for most of my variations, and have added my own base results for clarity e.g. '(T,T)'.

• ACE insertion/deletion ?
• CBS C699T (T,T) is rs234706.
• eNOS/NOS3 G894T (G,T) is rs1799983
• GSTM1 deletion ?
• GSTP1 A313G (A,G) is rs1695
• GSTP1 C341T (C,T) is rs1138272
• IL-6 G(-174)C (C,G) is rs1800795
• MTHFR 677C>T (C,T) is rs1801133
• PPARγ2 Pro12Ala (C,G) is rs1801282
• TNF-α G(-308)A (A,G) is rs1800629
• VDR Bsm1 (A,G) is rs1544410
• VDR Fok1+25920 (T,C) is rs2228570 (NB most web hits state C>T, not T>C, so maybe Scion/Cellf got this wrong)
• VDR Taq/TaqI (C,T) is rs731236

 

[Sea]

I now have the rs numbers for most of my variations, and have added my own base results for clarity e.g. '(T,T)'.

• ACE insertion/deletion ?
• CBS C699T (T,T) is rs234706.
• eNOS/NOS3 G894T (G,T) is rs1799983
• GSTM1 deletion ?
• GSTP1 A313G (A,G) is rs1695
• GSTP1 C341T (C,T) is rs1138272
• IL-6 G(-174)C (C,G) is rs1800795
• MTHFR 677C>T (C,T) is rs1801133
• PPARγ2 Pro12Ala (C,G) is rs1801282
• TNF-α G(-308)A (A,G) is rs1800629
• VDR Bsm1 (A,G) is rs1544410
• VDR Fok1+25920 (T,C) is rs2228570 (NB most web hits state C>T, not T>C, so maybe Scion/Cellf got this wrong)
• VDR Taq/TaqI (C,T) is rs731236

The ACE insertion/deletion doesn't track to one snp, although some of them are given a reference sequence number. To know your exact variation you would need to know what position you were tested for. It seems that it isn't important to know that though, all the insertion/deletion variations in this gene seem to be treated as having the same effect.

Possible results are I/I (insertion/insertion), I/D (insertion/deletion) or DD (deletion/deletion)
I am guessing the way your result is written that you have the heterozygous version - I/D

http://snpedia.com/index.php/Rs4646994

The GSTM1, GSTP1 and GSTT genes are important in detoxification of carcinogens, toxins and oxidants.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2049057/

GSTM1
http://www.genecards.org/cgi-bin/carddisp.pl?gene=GSTM1
"Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta.

This gene encodes a glutathione S-transferase that belongs to the mu class. The mu class of enzymes functions in the detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, by conjugation with glutathione.

The genes encoding the mu class of enzymes are organized in a gene cluster on chromosome 1p13.3 and are known to be highly polymorphic. These genetic variations can change an individual's susceptibility to carcinogens and toxins as well as affect the toxicity and efficacy of certain drugs.

Null mutations of this class mu gene have been linked with an increase in a number of cancers, likely due to an increased susceptibility to environmental toxins and carcinogens. Multiple protein isoforms are encoded by transcript variants of this gene. (provided by RefSeq, Jul 2008)"

http://snpedia.com/index.php/GSTM1

This gene is absent in around 50% of people. The heterozygous version is not as bad as a homozygous deletion. Also the role of GSTM1, GSTT1 and GSTP1 overlap somewhat so since you have a functional GSTT1 gene you are more protected.

Your 2 GSTP1 snps are both missense mutations (which means that the changed allele results in instructions for a different protein to be made) They are both implicated in raising the risk of allergies and asthma as well as the general compromised detox ability.
rs1695 has a prevalence of 32% but rs1138272 is relatively rare at 3%.

Your VDR Fok result is heterozygous. One allele is C the other is T. It doesn't matter which order it is written in although it is customary to see it as CT. The order it is written doesn't tell you anything about which allele is the original or changed version. There is some controversy in the research over the effect of each version of this snp and others in VDR.

In more in depth testing they do differentiate order because some things have more or less effect if they are on the same strand. For instance if you inherit one mutation on a gene from your mother and a different one on the same gene from your father that can have a different effect than if you inherited the two mutations from your mother. The first instance may give you compromised gene function on both alleles whereas the second scenario may give you one fully functional strand and one compromised. Results for these tests are written as separate results for allele one and allele two.

 

[MeSci]

Thanks very much for this info, @Sea. It's very useful and enlightening. I guess the GST problems could at least partly explain my extreme sensitivity to artificial perfumes, which I developed before getting obvious ME but did not have before. Some trigger must have got that started.

Re ACE, the document I downloaded from Nutrametrix suggests that the deletion is at intron 16, but maybe that's just the only one they test for? Sciona/Cellf give the variation tested for, and which I have, as 'II/DD'. I wonder whether it could be implicated in my hypertension, which appeared quite suddenly some years into ME but responds quite well to an ACE inhibitor, although it often still fluctuates wildly from one minute to the next.

Sciona/Cellf give the Caucasian prevalence of rs1138272 as 15.8%. What source gives it as 3%?

 

[Sea]

@MeSci
Yes I agree the GST variations could be the problem for your perfume tolerance. I have a deletion of the GSTT1 gene and have trouble with lots of chemicals.

DbSnp gives overall prevalence for rs1138272 as 3%. It gives prevalence in Europeans as higher. 9% for homozygous and 19% for heterozygous. I don't know your ethnic background so I just looked at the overall figure.

http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=1138272

For the ACEdel it is most likely the one in intron 16 that you were tested for. It is the most studied and has evidence for several different effects.

It is not a snp though (SINGLE nucleotide polymorphism). Intron 16 is a region in the ACE gene and the deletion is 287 (some research says 288) base pairs long. So it is not tied to a single rs number. Only gene sequencing can determine the exact mutation. Tests (like 23andme) that look only at variations of single nucleotides at specific positions can really only surmise an insertion or deletion.