I’m hoping someone reading this understands genetics better than me… I know from 23andme that I am homozygous for a mutation on the TNF gene (snp rs1800629, TNF 308). Apparently this is very rare and is associated with all sorts of fun health issues. Fortunately, other than celiac and PsA I’m in very good health! I’m not on any medicine currently for PsA… methotrexate didn’t work for me so I’m waiting for insurance to approve otezla. My question is… I wonder how tnf biologics will work on me if I overexpress TNF? (Not that I know for sure that I overexpress TNF, but apparently that’s what usually happens with this mutation.). I’m just thinking ahead… if I get to the point where my dr wants to try a biologic, should I mention this to him?
Well ugly feet, I’ve got no pride so I’ll dive in with what is very likely an idiot question. Can you humour me & explain how you know you’ve got this particular mutation and who or what is 23andme? I’m just being very nosey and my only excuse is that I was under the impression that all us PsA peeps overexpress tnf but maybe the terminology is tripping me up.
I suppose I’m thinking that if you have a rare mutation then actually your rheumy should be the first to know about it …
If I’ve got information that even might be useful, I always mention it - it’s a partnership so they should be told everything, even if you are not sure if it’s relevant (amazing what I’ve learnt that way).
From a quick search, there does appear like there at least one preliminary study indicating it may have an impact on anti-TNF effectiveness, though they have quoted additional letters (AA, GG, or GA) as differentiating response. You might be able to have a bit of a search yourself to decide if you think it might impact your choice of anti-TNF (responses seemed variable to the different TNF inhibitors).
Aha, so 23andme does genetic testing and analysis. Should have googled!
Genetics are a lot more complicated then it looks… And even then researchers know… There are so many factors… I would tell your doctor but if the mutation just gives a “higher chance” then that means there are other factors at play… my guess is they don’t know enough yet for this information to actually be helpful… But I do think the research 23 and me does will help out everyone in the future…
Haha, I’m sorry, Sybil, I should have explained that first! Yes, they do genetic testing for ancestry purposes but also are allowed (FDA) to give some health information. I have figured out how to look up mutations that they don’t report on, so I have a lot of data but no idea what it all really means. I dabble in researching it lol.
Thank you Jen. I am AA, whereas GG is considered the “wild type” or normal. Apparently those of us with the A allele (especially 2 copies) over express tnf. But I don’t even have high inflammation markers, which I would think I would have if I had too much TNF (is that right?) So maybe I have the mutation but it isn’t expressing itself in me. Genetics is fascinating, but very confusing!
It could be that you need another mutation they are not aware of somewhere… anywhere in your DNA before you start making the extra tnf … Or you do have another mutation and that’s the thing that stops you from making too much… Or 10 mutations…
Very true!
23 and me is pure quackery and BTW I do know a LOT about genetics. You can report it, but don’t be surprised if your doc looks at you like you have 3 eyes. Association is NOT causation I could go into a long disertation about statistics but essentially what 23 and me has done (soley for the purpose of driving sales) is using an inference process which is based on discovering subtle patterns in the correlation between traits and consequently by leaving out what is called the “triad process” creates a ton of untrustworthy causal inference.
@Cynthia explained much more gently than I, but she has got it…
I hate to mention that 23 and me LOVEs the word Homozygous. When an individual has two of the same allele, whether dominant or recessive, they are homozygous. By failure to be able to define whether or not they are dominate or recessive (because they don’t know, its entirely possible you have the exact OPPOSITE situation or no situation at all.
The same situation exists with their “geneological” data every human for example carries the same genetic code. By inference one could be any race or nationality depending on what data is looked at. Again they don’t know what the allele they are “discovering” mean. This area isn’t regulated and became the focus of their "gene testing after they were shut down the first few times.
In any event you can read about and add to your files the critical reasoning 23and Me doesn’t consider on a regular basis.
There has been a great deal fo research done on using “testing” to predict which Biologic has the best chance of working and its thought it MIGHT be a thing in the next few years. We were able to do it with cattle, but they have a much simpler genome to deal with.
There is no more use to 23 and me then those Facebook name tests… But they do use the DNA information for research…
tnt… I use the raw data NOT the 23andme “traits” features. I took my own raw data and was able to determine that I have 2 copies of the rare A allele. I won’t get into my whole history with using 23andme, but it came about because we discovered that my son has a genetic defect (that fortunately is very treatable), and he was referred to a Harvard trained pediatric geneticist at the University of Rochester. His genetics dr sees great value in home DNA tests, but says it’s important to discuss findings with a doctor (thus my original post). Anyhow, while certain traits 23andme reports on (hair curliness, etc) may be quackery based on associations and user surveys, the raw data is very useful. And they are FDA approved to report on numerous health conditions such as Huntingtons Disease. So I’m guessing they have passed rigorous evaluation for their process. It has been very accurate in testing my kids for the celiac gene (I have celiac), and since they all have the gene, their pediatrician tests them every year for celiac. So, basically, it’s been very very helpful to my family! And… I have 2 very close friends who found their biological families because of home DNA tests. That was huge for them.
tnt, please visit this page… this is my son’s doctor. At the bottom you will find a video where he discusses commercial DNA tests. (Is it ok to post links? If not, you can google him… Chin To Fong at the University of Rochester.)
23 And me tests something close to 500,000 varient pairs that came from the human genome project that started back in 1990. Of those varient pairs only 10 passed muster with the FDaA for approval. (Celiac isn’t one of them, that’s a specific test for HLA DQ 2 and 10 which is whole different thing. (BTW even then it only happens 10% of the time with the varient)
I know Dr Fong fairly well although mostly in regards to his work with cleft palate. Don’t confuse genomes with chromosomes or metabollic disorders. You need to listen to his tape again the methodology the labs use is fine. Well it is now… But he goes on to say the same I said earlier. We have a ton of data, a few associations but very very few causations. Even the ten approved by the FDA come with huge conditions “increased risk” is as far as it goes.
Yes, links are fine, UF. Now if you posted that link multiple times, we might think you were trying to drum up business for the Dr. 
and that wouldn’t be OK.
I’m just pointing out that it’s not exactly quackery as you said. There is value in the service, and more importantly there is much more value to come in the future. As Dr Fong said, this is in its infancy. But he also said there is value and I agree with him. Won’t it be amazing if someday we can take a $150 test and it helps us choose the best treatment option? If my participation helps us get to that point then I’m all in! (Again, I mostly use raw data, not the other features. This is how we were able to compare our expensive celiac gene tests to the results we got from 23andme. I know they don’t report on that disease.) Anyhow, I’ll give my dr the info (and the study Jen mentioned)… he may be fascinated… or he may roll his eyes lol.
May I ask a question… it sounds like you are either a research scientist and/or an MD, am I correct? I’ve always been impressed by the level of knowledge you share here.
He’s not saying it’s quackery… just that there is not much use to the information you get right now… A lot more research is needed before you can actually say anything about one specific person if you have their genome in front of you…
The testing is is fine. It’s 23 and me’s marketing that is the isdue. It becomes quackery when something of dubious value even based in truth is sold implying value. That’s why cons succeed. There is always an element of truth that matches someone s desires whether it is a free cruise or answers for a debilitating disease. Someday perhaps it may be of value but not yet, keep in mind Two trillion, five hundred billion possibilities exist and need to be difined for 23 and me testing to be of value. The genome mapping process ended a number of years ago and only 10 of the 2 and a half trillion possibilities have been determined and only with a 10% accuracy.
[quote=“tntlamb, post:10, topic:7747”]
23 and me is pure quackery
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He clearly did say it was quackery, which is why I got a little defensive.
Sorry… that quote didn’t copy correctly, but reread tnt’s first line of his first response to me. “23andme is pure quackery”
I happen to disagree, but that’s fine - it’s ok to disagree. I value everyone’s input, and I learn from everything I read here.
To pull it into perspective, you are 10,000 times more likely to win the powerball spending $150.00 on lottery tickets than to get meaningful data if you spend spend $150.00 on 23 and me genome mapping.
BTW there is already a test for what you are talking about. Its called HLA B-27. Has tou doc ordered it yet?