Birdlady Posted July 1, 2012 Report Share Posted July 1, 2012 I know there's been a lot of discussion about NET on the forums. I have searched through the old posts and I read through some of it!My question is have any of you ever been tested for mutations on the NET gene? This was never even brought up with me.A few months ago I got 23andme tested and I've been going through looking for anything that might give me some clues. Well somehow I overlooked the NET gene (also called SLC6A2). I realized last night I have a missense mutation on this gene. I'm looking at this wondering if this could be the cause of my POTS. Maybe I am jumping the gun here? I dunno, but if it's not specifically causing POTS certainly it must be doing something with norepinephrine. I'm calling my doctor tomorrow and letting him know of my discovery.For those who are into the technical stuff. I have the missense on V245I or rs1805066. My result is AG, where the A changes the protein sequence from a Valine to an Isoleucine. The specific mutation that was found in the family studied here is different than what I have found in my data. A457P [dbSNP:rs121918126) So of course it's not entirely clear cut or a sure thing. Unfortunately 23andme didn't test for the one in the study, so I can't compare.Who knows if this will turn out to be anything, but I really wish docs would do more testing to find the underlying causes... Quote Link to comment Share on other sites More sharing options...
issie Posted July 2, 2012 Report Share Posted July 2, 2012 Dana, hope you're on to something here. I know there is some sort of dysfunction in us with HyperPOTS and NE levels. Supressing my NE with my one med - has still been my best med to date and seems to help my high bp's and hr's. I will look into this some more tomorrow and see what I can figure out. Keep us posted. There must be a connection. I'll look to see if I have the same profile - have to not have brain fog ---and it's bad tonight. Issie Quote Link to comment Share on other sites More sharing options...
Birdlady Posted July 2, 2012 Author Report Share Posted July 2, 2012 (edited) Issie, Well while you are at it here's the RS Id's for the other missenses they check for. I don't have any of these ones, so if your result differs from mine, you might want to talk to your doc. If you get SNPtips and use firefox it would take you about 10 seconds to check if you have these... No brain power needed! rs5563 aka N292T AA is Normalrs5566 aka A369P GG is Normalrs5567 aka N375S/A375S AA is Normalrs5570 aka K463R/L463A AA is Normalrs5558 aka F528C/P528C TT is Normalrs5559 aka Y548H/T548H TT is Normalrs3743788 aka I549T TT is NormalIf you match these results above, then you do not have any mutations on those! I'm still wondering if anyone here has had the NET gene sequenced by Mayo, Vanderbilt or Cleveland Clinic? Surely if it's talked about as a potential cause, at least some of us have had this ruled out. Every study I've seen says people don't have mutations, so if I do, then I think that's significant.Any thoughts?Edited: To make it more clear what is normal. Edited July 2, 2012 by Dana Quote Link to comment Share on other sites More sharing options...
issie Posted July 2, 2012 Report Share Posted July 2, 2012 Dana,WHAT DOES IT MEAN???????? I don't have the first one you mentioned last night (I was GG) . . . . .But have ALLLLLLLL the other ones.Issie Quote Link to comment Share on other sites More sharing options...
sue1234 Posted July 2, 2012 Report Share Posted July 2, 2012 The big institutions actually look at the NET gene???? All I got from one of them is "you seem like you're handling it pretty well"(said because I carry a fold up lawn chair so I can sit at any moment and slump while I sit) and "let's Google POTS on the internet". WHY am I not getting adequate care and investigation? Quote Link to comment Share on other sites More sharing options...
issie Posted July 2, 2012 Report Share Posted July 2, 2012 The big institutions actually look at the NET gene???? All I got from one of them is "you seem like you're handling it pretty well"(said because I carry a fold up lawn chair so I can sit at any moment and slump while I sit) and "let's Google POTS on the internet". WHY am I not getting adequate care and investigation?Sue,We are doing this genetic testing on our own and figuring things out for ourselves. You can have a 23&me test done also. Then to figure it all out . . .is a whole other story. You can hire people to help with your genetic info when you get it. Or, you can start learning with the rest of us. It seems like Greek to me right this minute and is WAY over my head. But, I'm starting to get more answers. The testing cost $300.Issie Quote Link to comment Share on other sites More sharing options...
Birdlady Posted July 2, 2012 Author Report Share Posted July 2, 2012 If you match mine in the 2nd post and you are GG on the first one, then you are good. I'm going to edit my post above to make it more clear. I don't have any of the other missenses. There are lots 23andme doesn't test for though, so I'd have to get my gene sequenced. Good reason to reinstate my insurance! lolSue,As Issie said, we did 23andme direct to consumer genetic testing. I've been going through my results for the past 3 months when I finally came across this. This seems huge...This is the biggest discovery I have found thus far, but I still don't know what it all means. hahah! Quote Link to comment Share on other sites More sharing options...
sue1234 Posted July 2, 2012 Report Share Posted July 2, 2012 Thanks Issie. May have to do it soon. I guess I was saying what I said because Dana said:"I'm still wondering if anyone here has had the NET gene sequenced by Mayo, Vanderbilt or Cleveland Clinic? Surely if it's talked about as a potential cause, at least some of us have had this ruled out."I was thinking maybe others that went to these institutions might have had this looked at, where that was definitely not even looked at.I agree that if it could be a possible basis for what causes this, it SHOULD be tested! Why leave us for years without answers? Quote Link to comment Share on other sites More sharing options...
issie Posted July 2, 2012 Report Share Posted July 2, 2012 Okay, Dana. I do match you completely with the last few you listed and my first one is GG. So, there's no problem with this then?Issie Quote Link to comment Share on other sites More sharing options...
Birdlady Posted July 2, 2012 Author Report Share Posted July 2, 2012 With the ones tested by 23andme, then it looks like you are good. There are 8 or 9 not tested by 23andme, so we don't know about those ones. Can't completely rule it out.Okay, Dana. I do match you completely with the last few you listed and my first one is GG. So, there's no problem with this then?Issie Quote Link to comment Share on other sites More sharing options...
ramakentesh Posted July 3, 2012 Report Share Posted July 3, 2012 Refer to my new post are epigenetic mechanism. I believe they have identified the mechanism suppressing NET in many POTS patients but now the question is it compensatory or etiological? Quote Link to comment Share on other sites More sharing options...
Birdlady Posted July 4, 2012 Author Report Share Posted July 4, 2012 Yes this is very interesting and I read your thread. I wonder though is everyone with a mutation on the SLC6A2 gene, symptomatic with POTS? I think in the twin studies only one of them was highly symptomatic, right? Correct me if I am wrong there. If it was the mutation alone that was causing POTS, then they both should have had it. So I wonder if the mutation and another mechanism suppressing NET would explain the difference in phenotype.Epigenetics are an amazing concept that science is just not even close to understanding. We are at least 10-15 years out from it IMO....Refer to my new post are epigenetic mechanism. I believe they have identified the mechanism suppressing NET in many POTS patients but now the question is it compensatory or etiological? Quote Link to comment Share on other sites More sharing options...
CharmedLinz Posted July 4, 2012 Report Share Posted July 4, 2012 Huh very interesting.........Out of curiosity I looked up 23&me and there is no way with the cost.Do they say anything about the AIRE gene in that 23&me???Here is an interesting link about the NET gene and SLC6A2, you probably already found this stuff. Very interesting.http://ghr.nlm.nih.gov/gene/SLC6A2 Quote Link to comment Share on other sites More sharing options...
RichGotsPots Posted July 4, 2012 Report Share Posted July 4, 2012 Pretty soon there are new companies that will actually map the whole genome for under $1000. Maybe in the next 5 years and then we won't have to guess at markers we will see the whole picture, so I'm kinda waiting for that... Quote Link to comment Share on other sites More sharing options...
ramakentesh Posted July 4, 2012 Report Share Posted July 4, 2012 mapping the genome is fine but we are talking about epigenetic regulation of a gene - the gene is intact and but its transcription is abnormal. But if you looked at the DNA it would appear normal.Yes this is very interesting and I read your thread. I wonder though is everyone with a mutation on the SLC6A2 gene, symptomatic with POTS? I think in the twin studies only one of them was highly symptomatic, right? Correct me if I am wrong there. If it was the mutation alone that was causing POTS, then they both should have had it. So I wonder if the mutation and another mechanism suppressing NET would explain the difference in phenotype.Correct. The proband had lower standing blood pressure than her twin and worse symptoms of orthostatic intolerance. Its hard to say why this was the case. I know that when my blood pressure is higher I feel better for what ever reason. Net could be the result of POTS rather than a cause as well. Quote Link to comment Share on other sites More sharing options...
RichGotsPots Posted July 4, 2012 Report Share Posted July 4, 2012 Not sure but I would think a current mapping would include those epi modifications as well not just sequencing... Quote Link to comment Share on other sites More sharing options...
ramakentesh Posted July 4, 2012 Report Share Posted July 4, 2012 There is something called transcriptome genome sequencing that would look at this.Id suggest any POTS patients to spend the $20 on this article - Im reading it now and i feel like popping champagne. Quote Link to comment Share on other sites More sharing options...
Birdlady Posted July 4, 2012 Author Report Share Posted July 4, 2012 I think you are missing the point of my thread. I have something going on with the gene and you keep saying that the gene is normal. lolAlso I looked up the study again and I was wrong. The two twins were highly affected by POTS. Some of the other family members who carried the mutation had some symptoms of POTS, but not the full blown disease.http://www.nejm.org/...le&t=articleTop"Furthermore, in the current study, family members who had the mutation also had some of the physiologic and biochemical abnormalities detected in the proband and her twin sister, but none had the full-blown syndrome. Thus, other genetic or environmental factors must have contributed to the phenotype in the two affected women." You can have the mutation and not have POTS (good for any siblings who might carry a mutation) and I can't rule out the possibility that my mom could be the carrier as well.mapping the genome is fine but we are talking about epigenetic regulation of a gene - the gene is intact and but its transcription is abnormal. But if you looked at the DNA it would appear normal.Yes this is very interesting and I read your thread. I wonder though is everyone with a mutation on the SLC6A2 gene, symptomatic with POTS? I think in the twin studies only one of them was highly symptomatic, right? Correct me if I am wrong there. If it was the mutation alone that was causing POTS, then they both should have had it. So I wonder if the mutation and another mechanism suppressing NET would explain the difference in phenotype.Correct. The proband had lower standing blood pressure than her twin and worse symptoms of orthostatic intolerance. Its hard to say why this was the case. I know that when my blood pressure is higher I feel better for what ever reason. Net could be the result of POTS rather than a cause as well. Quote Link to comment Share on other sites More sharing options...
Birdlady Posted July 4, 2012 Author Report Share Posted July 4, 2012 This was a Christmas gift from my mom, so that's the only way I could afford it... hah! THey also raised the price a month of 2 ago, so that kind of stinks.I looked up the AIRE gene and there are only 18 SNP's tested. Have you ever had your genetics tested with all of the docs you've seen? You'd think they would have considered this optino by now. Huh very interesting.........Out of curiosity I looked up 23&me and there is no way with the cost.Do they say anything about the AIRE gene in that 23&me???Here is an interesting link about the NET gene and SLC6A2, you probably already found this stuff. Very interesting.http://ghr.nlm.nih.gov/gene/SLC6A2 Quote Link to comment Share on other sites More sharing options...
CharmedLinz Posted July 5, 2012 Report Share Posted July 5, 2012 Well you'd think that wouldn't you Dana..... seems fairly obvious to me and to you that I should be tested genetically especially with all the family similarities.I did just get the AIRE gene test, Docs figured out how to order it and get it covered, it's not back yet.The Genetic appointment is on order, a big-wig at Cleveland Clinic accepted my case and I have an appointment in December. Fingers crossed pretty please.Can you explain the 18 SNP's or give me a link explaining what that means.The genetic home reference only goes so far into breakdown of the genes.HUGS!!! Quote Link to comment Share on other sites More sharing options...
CharmedLinz Posted July 5, 2012 Report Share Posted July 5, 2012 Ok sorry but I'm going to add to the plate of things you all must read.Just happened across this by accident and thought it pertinent to this discussion.http://www.mthfrheds.com/ Quote Link to comment Share on other sites More sharing options...
Birdlady Posted July 5, 2012 Author Report Share Posted July 5, 2012 All of this is soo confusing, so don't feel bad at all! SNP is short for Single-nucleotide polymorphism... Only 18 are tested for, which is not many at all. I couldn't even begin to guess how many SNP's are on a gene. Lots more than that... If you got the gene sequenced, then that is far better than just a mere 18 SNPs! Genotyping is the cheap man's method of genetic testing. It is the full sequences that will be what's next to come and as Rich said in the next few years they are saying under a $1000. The problem though is going to be interpretation....HA! There was an exome pilot on 23andme for $1k and it is insanely confusely what these people are getting as results. I wouldn't even know where to begin. It took me 3 months to figure out I had this stupid SNP sitting in my data and this is just a genotyping! Exome data is like a zipped 16 GB's! Compare that to a tiny 24MB txt file!! hahahLots of people are getting into the methylation, MTHFR stuff right now. I think for some this could be helpful if you have a homozygous mutation or are what they call compound heterozygous for the two common MTHFR mutations (C677T and A1298C). I know people who are homozygous for these mutations and aren't sick and I know people who don't have MTHFR mutations and are sick, so it's defiinitely not as clear cut as some of these sites try to suggest. I have seen this website linked a few places and the info is very interesting and food for thought.These mutations on MTHFR gene are quite common though. Homozygous C677T and A1298C mutations are seen in ~11% of the population. I think it is probably far higher than that though and as genetic testing becomes cheaper and cheaper, I think we will see it is extremely common in the general public. A few years ago I had tried supplementing with the different B vitamins and it just made me feel worse off, but that's me and I react strangely to things all the time...HAH!! Quote Link to comment Share on other sites More sharing options...
RichGotsPots Posted July 5, 2012 Report Share Posted July 5, 2012 Finding gene issues are amazing don't get me wrong, because then we can actually get targeted gene therapies. The only problem is all of those therapies are light years from ever happening because we are small orphans in a pool of monster drugs like for cancers,obesity, heart disease. That's why we are literally only getting borrowed medicine for tachy, or hypertension or anxiety... We don't even have a recommended list of beta blockers. There are literally at least 20 beta blockers on the market, if I did a poll on here I bet ppl have tried all 20 plus ivabridine... So even if there is one gene or epigenetic mod to point to, how it is it cause such random symptoms in us. Especially those of us whose symptoms evolve or change. So would the gene therapy, block any more modifications, or does it repair the gene and what pharm company would even fund such an orphan drug... Sorry to sound so down, just in a hurry for answers lol Quote Link to comment Share on other sites More sharing options...
issie Posted July 5, 2012 Report Share Posted July 5, 2012 There is something called transcriptome genome sequencing that would look at this.Id suggest any POTS patients to spend the $20 on this article - Im reading it now and i feel like popping champagne.Somehow, I missed what article you're talking about. Can you give a link? What makes it a celebration ---pray tell.......Issie Quote Link to comment Share on other sites More sharing options...
Birdlady Posted July 5, 2012 Author Report Share Posted July 5, 2012 Well if I find out it is a gene causing POTS, then I can stop looking for other things. I don't expect them to have gene therapy any time soon. I guess my excitement about finding this is because I spend a lot of my days researching and I'm getting pretty sick of it. I just want some peace in my life away from medical journals, studies and forums...lol I dunno if that's how any of you feel, but I'm getting pretty sick of looking at medical stuff. Realistically though, I just don't think in our lifetimes they will be curing POTS. There are so many other diseases out there that actually kill you they can't cure.Issie, the study Rama is talking about is the one you emailed me about epigenetics.http://atvb.ahajourn...244343.abstractI asked my brother to see if he could get the study and he said it's not available at his university unfortunately. Have to pay for it. $20 could buy food, so that's not happening here. Maybe I can ask my cardiologist if he can get it.Finding gene issues are amazing don't get me wrong, because then we can actually get targeted gene therapies. The only problem is all of those therapies are light years from ever happening because we are small orphans in a pool of monster drugs like for cancers,obesity, heart disease. That's why we are literally only getting borrowed medicine for tachy, or hypertension or anxiety... We don't even have a recommended list of beta blockers. There are literally at least 20 beta blockers on the market, if I did a poll on here I bet ppl have tried all 20 plus ivabridine... So even if there is one gene or epigenetic mod to point to, how it is it cause such random symptoms in us. Especially those of us whose symptoms evolve or change. So would the gene therapy, block any more modifications, or does it repair the gene and what pharm company would even fund such an orphan drug... Sorry to sound so down, just in a hurry for answers lol Quote Link to comment Share on other sites More sharing options...
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