SNPs for Nitric Oxide Synthase (NOS3) - alternative(s) to Yasko's marker

[nandixon]

23andMe doesn't provide the SNP marker for dysfunction in the endothelial nitric oxide synthase (NOS3) enzyme that Yasko uses, i.e., D298E (rs1799983). They do however give data for some 30+ other SNPs, including rs2070744. (https://www.23andme.com/you/explorer/gene/?gene_name=nos3) This SNP, while not a proxy/substitute for Yasko's, appears to be functionally as important, and might suggest the need for ammonia support/neutralization where the risk allele is present. A number of other SNPs reported by 23andMe may be significant as well.

So other people can check their results, here are the SNPs currently found on SNPedia for NOS3 (http://www.snpedia.com/index.php/NOS3) with my personal results and the "normal" (common) alleles in parentheses. Where I'm homozygous for the risk allele (+/+) I've also made some notations and given the percentage frequency of occurrence in the general population using the data from openSNP. I think I double-checked all my homozygous results against the actual research articles that SNPedia cited, so hopefully this is pretty accurate.

I had delayed looking into my NOS3 results because when I first checked them, all 30+ were showing as homozygous and so I figured I was fairly safe. That was not a good assumption:

rs11771433 No Data
rs1799983 No Data (Yasko marker D298E)
rs1800779 +/+ GG (AA) (associated w/ hypoxic-ischemic encephalopathy; 17% frequency)
rs180783 +/+ AA (TT) (proxy for rs4496877 - see below; 17% frequency)
rs2070744 T(-786)C +/+ CC (TT) (major issues w/ ammonia detoxification if similar to D298E => take yucca with meals and activated charcoal at bedtime; significantly lower promoter of endothelial NOS => reduced nitric oxide production; increased risk of rheumatoid arthritis, bladder cancer, progression of prostate cancer; 13% frequency)
rs3918188 -/- CC (CC)
rs3918226 -/- CC (CC)
rs3918227 -/- CC (CC)
rs4496877 +/+ AA (GG) (significantly increased nephropathy risk in type-1 diabetes; 13% frequency)
rs743507 +/+ CC (TT) (significant association w/ diabetic nephropathy; 7% frequency)
rs7830 -/- GG (TT)

 

[merylg]

NOS3 150689397 rs1800783 A or T AT

NOS3 150689943 rs1800779 A or G AG

NOS3 150689970 rs2243311 C or T CC

NOS3 150690079 rs2070744 C or T CT

NOS3 150690176 rs3918226 C or T CC

NOS3 150695726 rs1549758 C or T CC

NOS3 150699877 rs2853792 A or G AA

NOS3 150700946 rs3918227 A or C CC

NOS3 150702219 rs3918184 C or T CC

NOS3 150702331 rs3918185 A or G GG

NOS3 150702432 rs3918186 A or T AT

NOS3 150702591 rs3918187 A or G AA

NOS3 150702781 rs3918188 A or C CC

NOS3 150703041 rs2566511 C or T no call

NOS3 150703130 rs3918229 C or T CC

NOS3 150703242 rs2853795 A or G AG

 

[merylg]

NOS3 150703414 rs2566513 G or T TT

NOS3 150703915 rs2853796 G or T GT

NOS3 150704843 rs891511 A or G AA

NOS3 150705413 rs3918230 C or G GG

NOS3 150705842 rs3918196 A or G GG

NOS3 150706383 rs753482 A or C AA

NOS3 150706640 rs3918232 A or G GG

NOS3 150706915 rs743506 A or G AA

NOS3 150707117 rs3730009 C or T TT

NOS3 150707344 rs3918201 G or T GG

NOS3 150707488 rs743507 C or T TT

NOS3 150707943 rs867225 A or G GG

NOS3 150708089 rs891512 A or G GG

NOS3 150708302 rs1808593 G or T TT

NOS3 150708923 rs3918235 A or G GG

NOS3 150709291 rs3918236 A or G GG

NOS3, ATG9B 150709571 rs7830 G or T TT

NOS3, ATG9B 150709904 rs3918208 C or T TT

NOS3, ATG9B 150710907 rs3918211 C or T TT

intergenic 150680506 rs4496877 G or T GT

 

[nandixon]

Thanks Meryl! I've combined our total 23andMe results together below (mine first, your's second in each line) and corrected two transcription errors made in my original post above. [Where I typed "rs4496877 +/+ AA (GG)," the "AA" should have been TT. And where I typed "rs7830 -/- GG (TT)," the "TT" should have been GG.]

NOS3:
rs1800783 T>A AA (++), AT (+-) fn1
rs1800779 A>G GG (++), AG (-+) fn2
rs2243311 C>T CC (--), CC (--)
rs2070744 T>C CC (++), CT (+-) fn3
rs3918226 C>T CC (--), CC (--)
rs1549758 C>T TT (++), CC (--) fn4
rs2853792 A>G GG (++), AA (--) fn5
rs3918227 C>A CC (--), CC (--)
rs3918184 C>T CC (--), CC (--)
rs3918185 G>A GG (--), GG (--)
rs3918186 A>T AA (--), AT (-+)
rs3918187 A>G AA (--), AA (--)
rs3918188 C>A CC (--), CC (--)
rs2566511 C>T CC (--), no call
rs3918229 C>T CC (--), CC (--)
rs2853795 A>G AA (--), AG (-+)
rs2566513 T>G TT (--), TT (--)
rs2853796 G>T GG (--), GT (-+)
rs891511 G>A GG (--), AA (++) fn6
rs3918230 G>C GG (--), GG (--)
rs3918196 G>A GG (--), GG (--)
rs753482 A>C CC (++), AA (--) fn7
rs3918232 G>A GG (--), GG (--)
rs743506 A>G GG (++), AA (--) fn8
rs3730009 T>C TT (--), TT (--)
rs3918201 G>T GG (--), GG (--)
rs743507 T>C CC (++), TT (--) fn9
rs867225 G>A GG (--), GG (--)
rs891512 G>A AA (++), GG (--) fn10
rs1808593 T>G GG (++), TT (--) fn11
rs3918235 G>A GG (--), GG (--)
rs3918236 G>A GG (--), GG (--)
rs7830 G>T GG (--), TT (++) fn12
rs3918208 T>C TT (--), TT (--)
rs3918211 T>C TT (--), TT (--)
rs4496877 G>T TT (++), GT (-+) fn13

Footnotes (fn):
1 Proxy for rs4496877 (see fn13); 17% frequency
2 Associated w/ hypoxic-ischemic encephalopathy; 17% freq
3 Major issues w/ ammonia detoxification if similar to Yasko's D298E (rs1799983) => might take yucca with meals and activated charcoal at bedtime; significantly lower promoter of endothelial NOS => reduced nitric oxide production; increased risk of rheumatoid arthritis, bladder cancer, progression of prostate cancer; 13% freq
4 Possible association w/ Parkinson's Disease; increased susceptibility to steroid-induced osteonecrosis of femoral head (ONFH); may be linked with Yasko's marker; 8% freq
5 Significance?; 19% freq
6 Significance?; 13% freq
7 High risk of restenosis and cardiovascular events in type-2 diabetes; 4% freq
8 Relation in migraine; 9% freq
9 Significant association w/ diabetic nephropathy; 7% frequency
10 Associated w/ hypertension in type-2 diabetes; 4% freq
11 Associated w/ hypoxicischemic encephalopathy and acute mountain sickness; 7% freq
12 Significant association w/ "ABI" marker for peripheral arterial disease; 11% freq
13 Significantly increased nephropathy risk in type-1 diabetes; 13% freq

 

[roxie60]

is 'no call' when they dont give you letters for the SNP just -- ?

 

[roxie60]

Hi nan, I was wondering are the footnotes in relation to the 'common' SNP or the 'uncommon' SNPs?

e.g. 13Significantly increased nephropathy risk in type-1 diabetes; 13% freq - this applies to the 'uncommon variety which would be TT, am I reading/interpreting this correctly?

what is the source for your footnotes?

 

[roxie60]

Note as of 1/9/2013 there are 35 NOS3 SNPs from 23andMe (incase this changes overtime as we have seen with other SNPs).

 

[roxie60]

I have added mine to the list. Also added the tracking convention used in other threads I think is helpful. I have copied a dup of the list cause my OCD is kicking in and I like to see things line up as best possible. Use which ever one you want to add new data. I wonder if we should put 'common' = 1 with orientation in parentheses? Just an organization suggestion, did not change what you started nan, just addded mine and the tracking row. My values are in red.

1=nandixon, 2=merylg, 3=roxie60

NOS3:
rs1800783 T>A... AA (++), AT (+-) , TT(--)fn1
rs1800779 A>G... GG (++), AG (-+), AA(--) fn2
rs2243311 C>T.... CC (--), CC (--), CC(--)
rs2070744 T>C.... CC (++), CT (+-), (--, no call?) fn3
rs3918226 C>T.... CC (--), CC (--), CC (--)
rs1549758 C>T.... TT (++), CC (--), CC (--) fn4
rs2853792 A>G... GG (++), AA (--), AA (--), fn5
rs3918227 C>A... CC (--), CC (--), CC (--),
rs3918184 C>T.... CC (--), CC (--), CT (-+),
rs3918185 G>A... GG (--), GG (--), GG(--)
rs3918186 A>T.... AA (--), AT (-+), AA(--)
rs3918187 A>G... AA (--), AA (--), AA(--)
rs3918188 C>A... CC (--), CC (--), AC(+-)
rs2566511 C>T.... CC (--), no call, CT(-+)
rs3918229 C>T.... CC (--), CC (--), CC(--)
rs2853795 A>G... AA (--), AG (-+), AG(-+)
rs2566513 T>G.... TT (--), TT (--), TT(--)
rs2853796 G>T.... GG (--), GT (-+), TT(--)
rs891511 G>A..... GG (--), AA (++), AG(+-) fn6
rs3918230 G>C... GG (--), GG (--), GG (--)
rs3918196 G>A... GG (--), GG (--), GG (--)
rs753482 A>C..... CC (++), AA (--), AA(--) fn7
rs3918232 G>A... GG (--), GG (--), GG(--)
rs743506 A>G..... GG (++),AA (--), AA(--) fn8
rs3730009 T>C.... TT (--), TT (--), TT(--)
rs3918201 G>T.... GG (--), GG (--), GG(--)
rs743507 T>C...... CC (++),TT (--), TT(--) fn9
rs867225 G>A..... GG (--), GG (--), GG(--)
rs891512 G>A..... AA (++),GG (--), GG(--) fn10
rs1808593 T>G.... GG (++),TT (--), TT(--) fn11
rs3918235 G>A.... GG (--), GG (--), GG(--)
rs3918236 G>A.... GG (--), GG (--), GG(--)
rs7830 G>T.......... GG (--), TT (++), GT(-+) fn12
rs3918208 T>C.... TT (--), TT (--), TT(--)
rs3918211 T>C.... TT (--), TT (--), TT(--)
rs4496877 G>T.... TT (++),GT (-+), GG(--) fn13

Footnotes (fn):
1 Proxy for rs4496877 (see fn13); 17% frequency
2 Associated w/ hypoxic-ischemic encephalopathy; 17% freq
3 Major issues w/ ammonia detoxification if similar to Yasko's D298E (rs1799983) => might take yucca with meals and activated charcoal at bedtime; significantly lower promoter of endothelial NOS => reduced nitric oxide production; increased risk of rheumatoid arthritis, bladder cancer, progression of prostate cancer; 13% freq
4 Possible association w/ Parkinson's Disease; increased susceptibility to steroid-induced osteonecrosis of femoral head (ONFH); may be linked with Yasko's marker; 8% freq
5 Significance?; 19% freq
6 Significance?; 13% freq
7 High risk of restenosis and cardiovascular events in type-2 diabetes; 4% freq
8 Relation in migraine; 9% freq
9 Significant association w/ diabetic nephropathy; 7% frequency
10 Associated w/ hypertension in type-2 diabetes; 4% freq
11 Associated w/ hypoxicischemic encephalopathy and acute mountain sickness; 7% freq
12 Significant association w/ "ABI" marker for peripheral arterial disease; 11% freq
13 Significantly increased nephropathy risk in type-1 diabetes; 13% freq

 

[roxie60]

not sure what happened to formatting, maybe I hit a limit. Will try and edit post to fix formatting where last few SNPs ended up in one line

 

[roxie60]

Here is the list without orientation (although I think that is important to understand and make observations) to make room for other members data, if you want or continue to use format with orientation.

1=nandixon, 2=merylg, 3=roxie60

NOS3:
rs1800783 T>A... AA, AT, TT, fn1
rs1800779 A>G... GG, AG, AA, fn2
rs2243311 C>T.... CC, CC, CC,
rs2070744 T>C.... CC, CT, (--, no call?) fn3
rs3918226 C>T.... CC, CC, CC,
rs1549758 C>T.... TT, CC, CC, fn4
rs2853792 A>G... GG, AA, AA, fn5
rs3918227 C>A... CC, CC, CC,
rs3918184 C>T.... CC, CC, CT,
rs3918185 G>A... GG, GG, GG,
rs3918186 A>T.... AA, AT, AA,
rs3918187 A>G... AA, AA, AA,
rs3918188 C>A... CC, CC, AC,
rs2566511 C>T.... CC, no call, CT,
rs3918229 C>T.... CC, CC, CC,
rs2853795 A>G... AA, AG, AG,
rs2566513 T>G.... TT, TT, TT,
rs2853796 G>T.... GG, GT, TT,
rs891511 G>A..... GG, AA, AG, fn6
rs3918230 G>C... GG, GG, GG,
rs3918196 G>A... GG, GG, GG,
rs753482 A>C..... CC, AA, AA, fn7
rs3918232 G>A... GG, GG, GG,
rs743506 A>G..... GG, AA, AA, fn8
rs3730009 T>C.... TT, TT, TT,
rs3918201 G>T.... GG, GG, GG
rs743507 T>C...... CC,TT, TT, fn9
rs867225 G>A..... GG, GG, GG,
rs891512 G>A..... AA,GG, GG, fn10
rs1808593 T>G.... GG,TT, TT, fn11
rs3918235 G>A.... GG, GG, GG,
rs3918236 G>A.... GG, GG, GG,
rs7830 G>T.......... GG, TT, GT, fn12
rs3918208 T>C.... TT, TT, TT,
rs3918211 T>C.... TT, TT, TT,
rs4496877 G>T.... TT,GT, GG, fn13

Footnotes (fn):
1 Proxy for rs4496877 (see fn13); 17% frequency
2 Associated w/ hypoxic-ischemic encephalopathy; 17% freq
3 Major issues w/ ammonia detoxification if similar to Yasko's D298E (rs1799983) => might take yucca with meals and activated charcoal at bedtime; significantly lower promoter of endothelial NOS => reduced nitric oxide production; increased risk of rheumatoid arthritis, bladder cancer, progression of prostate cancer; 13% freq
4 Possible association w/ Parkinson's Disease; increased susceptibility to steroid-induced osteonecrosis of femoral head (ONFH); may be linked with Yasko's marker; 8% freq
5 Significance?; 19% freq
6 Significance?; 13% freq
7 High risk of restenosis and cardiovascular events in type-2 diabetes; 4% freq
8 Relation in migraine; 9% freq
9 Significant association w/ diabetic nephropathy; 7% frequency
10 Associated w/ hypertension in type-2 diabetes; 4% freq
11 Associated w/ hypoxicischemic encephalopathy and acute mountain sickness; 7% freq
12 Significant association w/ "ABI" marker for peripheral arterial disease; 11% freq
13 Significantly increased nephropathy risk in type-1 diabetes; 13% freq

 

[roxie60]

I think it is important that we add 'common and orientation as the first entry in all the SNPs data we are trying to capture so people at a glance can see where they stand, what do you think?

 

[roxie60]

Dont know if this effort will amount to much. It seems we should only record data from 23andMe since there is a risk other data is using info from different location of the gene. Feels like a rabbit hole or back hole. I know we want answers but wondering if we are the ones that will figure it all out...hum

 

[Leon]

23andMe doesn't provide the SNP marker for dysfunction in the endothelial nitric oxide synthase (NOS3) enzyme that Yasko uses, i.e., D298E (rs1799983). They do however give data for some 30+ other SNPs, including rs2070744. (https://www.23andme.com/you/explorer/gene/?gene_name=nos3) This SNP, while not a proxy/substitute for Yasko's, appears to be functionally as important, and might suggest the need for ammonia support/neutralization where the risk allele is present. A number of other SNPs reported by 23andMe may be significant as well.

rs2070744 T(-786)C +/+ CC (TT) (major issues w/ ammonia detoxification if similar to D298E => take yucca with meals and activated charcoal at bedtime; significantly lower promoter of endothelial NOS => reduced nitric oxide production; increased risk of rheumatoid arthritis, bladder cancer, progression of prostate cancer; 13% frequency)

Thank you for posting this nandixon - I'm homozygous for the C allele.

I can find reference to rheumatoid arthritus (which is very interesting, given my maternal grandmother was housebound from a young age due to this) and cardiovascular risk; but I can't find any reference to ammonia issues. I'm certain I have ammonia issues (e.g. I can't currently eat animal/fish protein or ingest glutamine). Have you had any more thoughts about whether this is a useful marker for the rs1799983 SNP?

 

[roxie60]

Does '--' on that SNP mean I dont have it or they couldnt figure it out?

 

[Valentijn]

Does '--' on that SNP mean I dont have it or they couldnt figure it out?

Yes

It can mean either of those. Or that the chip they used to process your sample doesn't test for that SNP.