DNA Direct and deCODE Offering TCF7L2 Genetic Testing for Type 2 Diabetes
Knowing more about your risk of type 2 diabetes is just a keyboard click away at DNA Direct. Together with deCODE diagnostics, DNA Direct is now offering deCODE T2, a genetic test that examines the presence of the “T” allele of SNP rs7903146, located within the transcription factor 7-like 2 (TCF7L2) gene. Almost twice as many people with type 2 diabetes have two copies of the TCF7L2 gene variant. As far as I can tell, the SNP is not known to cause a functional change in the activity of the gene, but is associated with reduced insulin secretion.
Kari Stefansson, CEO of deCODE:
Understanding one’s risk of T2D is the first step toward enabling more effective prevention. The principal risk factors for T2D are well known – obesity, unhealthy diet and lack of exercise – and by addressing these individuals can reduce their risk of becoming diabetic. Family history, part of which involves genetic risk factors, also plays a part. deCODE T2(TM) offers a new tool to help individuals and their doctors bring an
understanding of inherited risk into the picture. deCODE T2(TM) is but the first of several DNA-based predisposition tests we have in development for common diseases. We believe that as individuals, doctors and healthcare providers begin to integrate these tests as a part of everyday healthcare – much as cholesterol screening has become a part of understanding and
reducing risk of heart disease – these tests may provide major benefit to public health
Given that type 2 diabetes is a multifactorial disease caused by many different genetic and lifestyle factors, having one genetic test done on one specific gene variant may not tell you much about your risk of type 2 diabetes. If you test positive, your risk of developing type 2 diabetes is twice as high as someone who does not have two copies of the TCF7L2 gene variant but your risk still depends on other risk factors such as weight, lifestyle habits, diet, and other genetic variants. In a clinical trial studying prediabetics, those who have two copies of the TCF7L2 gene variant of interest could reduce their risk of type 2 diabetes through weight loss. These individuals may also benefit from metformin to increase insulin response.
For the informed person, this type of limited genetic information can be empowering. But, please don’t be deluded into thinking that you’re not at risk if you test negative. It takes more than one $500 genetic test to develop a truly accurate health profile.
Hsien Hsien,
I am blown away that they would market this test. They have good replication, but one test a risk profile does not make! If their not careful, DNA Direct will end up on quackwatch.com! They need some better medical advice. My partner warned them about these things a year ago!
-Steve
http://www.thegenesherpa.blogspot.com
I’ll bet every genetic counselor in the world is horrified at this. Spending 500 dollars to figure out that you are twice as likely to end up with Type 2 diabetes than someone else? And since there is nothing known about why this is there isn’t anything specific you can do about it. Just exercise more and eat better.
Reminds me a bit of the old ApoE4 test that used to be done for Alzheimer’s. You could find out you were at higher risk but beyond trying to do more crosswords and Sudoku, there wasn’t much you could do. We have a couple of great videos in our Genetics exhibit at The Tech in San Jose CA on this subject that really drive this point home.
Steve: lol @ quackwatch.com If people take the time to read the information on the DNA Direct site and/or talk to the company’s genetic counselors, they should be alright. The trouble comes from assumptions and misinformation.
Barry: Hi there! So pleased to see you here. We love The Tech museum in San Jose.
The thing is, genetic testing is never going to be 100% except for the rarest of diseases. For some people, a test like this could help jolt them into doing something about their lifestyle. If they’ve got the money, why not? Most people won’t have $500 lying around to do this and, hopefully, those who are willing the spend the cash are motivated to learn more about genetics and health.
Hsien Hsien,
I agree that testing certainly has a way of motivating behaviour. My only problem is that the results of a “negative” test also have the same impact. Oh, I won’t get diabetes. So
a. I don’t need to watch my weight
b. I shouldn’t worry about that diagnosis of pre-diabetes
c. I can stop taking my metformin
That is the damage we create without properly educating those doing testing. I hope you don’t leave genetics or “genetics and health” I love your posts.
-Steve
http://www.thegenesherpa.blogspot.com
I am torn about all of this as well. I hadn’t properly appreciated it all until I saw the APOE4 video. The woman was tested and found she was homozygous. So she kne she passed it on to her kids. She had a lot of trouble dealing with the guilt of it all.
Type 2 diabetes might not be so bad as long as they understand the difference between, say, Type 1 and Type 2 diabetes. I’d hate for a parent to feel guilty because they have the mutation and their child ends up with Type 1 diabetes.
Wow – Glad to see this new test has everyone talking. As you can imagine, I have a lot to say about deCODE’s new TCF7L2 test but I’ll try to keep it short. First, this test, like so many risk tests before it (Hemochromatosis, Thrombophilia, BRCA1-2) is about RISK. This means that pre-test education and results interpretation is key.
What I have experienced in 15+ years of consumer/patient education is that people are intelligent and self-focused. Tell them what something means for them individually, and they get it. If you talk plainly about independent and compound risks as they relate to an individual — i.e.
“your weight, your genes, your family history which is x, y, z” — people do understand.
Second, not everyone is motivated by information. But with a price point of $500, I expect this test will be used only by people who are active and educated healthcare consumers — those who understand what the test can/can’t tell you, and who want to test in order to make more informed choices. These are the kind of people who seek genetic counseling.
From my understanding of the research (see DPP and DREAM trials), people who might benefit most from the test are prediabetics who are making choices about how aggressive to treat the prediabetes. This test provides one more piece of info about their risk — and could make the difference between medicating or not.
Lastly, as it happens I met an Ob/Gyn last night who practices in a rural area and provides more than just Ob/Gyn care. She was very
excited about the test and thought it would be “the nail in the coffin” that can get people “off their butt” to do something about their risk. Her only concern was insurance coverage — without it, she feels people won’t test. I know of other physicians (internists) who are also excited about the test.
Barry, the APOE comparison doesn’t work for me. The two conditions — their risk constellation, etiology, the role the genes/variants play in the disease etiology, and preventive/treatment measures — are very different. I think Stefansson’s comparison to cholesterol/heart disease is somewhat closer.
Ah, now I guess I need to go post about this at my own blog…
One other thought: Steve, please check out our site’s info about the deCODE T2 test (TCF7L2) and feel free to email me directly. Do you think we adequately convey the concept of risk? Do we clearly address your concerns about people receiving negative results?
Here’s the consumer-oriented channel: deCODE T2
Here’s our channel for physicians: deCODE T2
I’m at lisa@dnadirect.com
And a very last comment. The population study on TCF7L2 “T” homozygotes in the US showed an almost 3-fold risk. What does that say about us compared to the rest of pop/ethnic groups studied?
Can you say enviro-genome interaction? The western diet is spreading, so is methylation and trans fat
Thanks for the offer to edit the site. Unfortunately, I have to decline due to liability. That malpractice keeps getting more expensive
-Steve
http://www.thegenesherpa.blogspot.com
Still, 500 dollars to find out that you are at 2-fold risk for type 2 diabetes doesn’t seem like a good deal. I am still struggling with what I don’t like about this.
Another concern I have is when people get the negative result and head straight to McDonalds. I even fell into this trap.
For fun, I had my family’s MC1R gene sequenced (this was for a possible project at The Tech). My wife, son and I are carriers, my redhead son has two copies and my daughter doesn’t have any red hair alleles.
Being a carrier is an increased risk for sun cancer and I was talking with my wife about this. I said our daughter doesn’t have the red hair MC1R allele so we don’t need to be as vigilant about sunscreen with her. My wife correctly pointed out that this was one single factor for skin cancer risk and we will continue to be vigilant.
I worry people will get this genetic test, get the negative result, and come to the not-so-clever interpretation I did…
The discussion has taken an interesting turn. I think we assume lowest common denominator when it comes to consumers’ understanding of DNA tests. I believe most people do search out detailed information when they undergo genetic testing simply because it’s not something that’s common and everyday (yet). I receive emails occasionally asking me about the accuracy of paternity tests which tells me even a test that isn’t necessarily all that complicated makes people ask questions.
When it comes to susceptibility gene testing, I believe most people will understand the limited meaning of the the test. Even though you, Barry, became rather lax about the sunscreen, I’m sure you wouldn’t have advised your daughter to go bake herself in the sun just because she didn’t have a copy of the MC1R gene variant. (There are wrinkles to worry about too!
)
Although I haven’t gone through the DNA testing procedure at DNA Direct, the fact that they have genetic counselors on staff whom you can email and call is reassuring. Their materials are also meticulously researched and written so as long as a consumer assumes the responsibility (which they always should!) of reading the fine print, they should get a good idea of what to do with their results.
If the market will bear genetic testing at this stage, then I believe consumers have the right to purchase them. Let’s not turn ourselves into a nanny state. Caveat emptor.
I promise I’ll shut up after this but I do want to comment on the nanny state. I agree we don’t want a nanny state but we do want some regulation. We don’t want formaldehyde in our canned goods (ala the 19th century), child labor etc. So there needs to be some regulation. The question is where.
Seat belts? Child safety seats? Motorcycle helmets? Expensive genetic tests that may not be all that helpful? Where to draw the line, that is the question.
Barry: Oh, no! Please don’t shut-up. I like it when people talk.
Of course you’re right that some degree regulation is necessary. But comparing all of those things to genetic testing is sorta…extreme!! The impact of these $500 genetic tests on public health is going to be limited for now. I don’t know how many tests deCODE and DNA Direct expect to sell but it certainly does not compare to the number of people who get in cars or ride motorcycles.
No, you’re right, my examples were a bit extreme. What about herbs that may or may not do a patient good? I just hate to see people pay for something that won’t be as useful as they think.
Barry: Herbs… Supplements… That’s a whole ‘nother kettle of fish! I actually don’t care if people waste their money because we all waste money in some way. (I am not going to admit what I waste my money on!)
Money’s money. Some people have it to spent on genetic testing and others on bulk vitamins from Costco. Who are we to say what they should spend it on! To some extent (or more!), we’re responsible for accessing accurate information and making our own judgment.
All true but I am not sure DNA Direct likes where this conversation is going! Let people keep the right to waste their money on genetic tests that won’t be that helpful for them…
Barry: I don’t think it’s fair to say that susceptibility gene testing won’t be helpful for anyone. Some people are simply curious about their DNA and others need a kick in the butt to get them moving. As long as the proper emphasis is placed on the relative importance of the results, I think and hope that it will be a matter of information gathering for most people.
I didn’t mean that it wouldn’t be helpful for ANYONE. I am always curious about what DNA I have from being a biologist. I suppose if the page is really written well to strongly indicate that this gene is one of many and that the negative result does not mean you are now Type 2 diabetes risk free, and that the positive result means that you are at slightly higher risk and will not get the disease for sure, it would be OK for people with an extra 500 dollars to be allowed to spend it on the test. I just would want people to really understand what the test can offer them. I’d like to see a disclaimer like this just before they hit the confirm button on the sale as well.
Barry’s point is well taken. At least by myself. I personally had a patient whom was told by his GI doctor that his FAP would be cured if his colon was taken out. 15 years later he developed ampullary carcinoma and expired in my ICU. During that time he had a child who was 1 at his time of death. They could have done PGD but there was no continuity of care. More importantly no genetic counseling. What comes of the “negative test” in this curious patient? What if the risk changes? What if literature shows that a new medication can be beneficial? Who follows that up? DeCODE? DNADirect? I sure know that the PMD probably doesn’t even know what TCF7L2 means…..
-Steve
http://www.thegenesherpa.blogspot.com
Lastly, a new study finds even more genes related to DM2. Perhaps I could spend 3500 USD to refine risk to the level of what a 3 generation pedigree can do. Take a look. http://www.cnn.com/2007/HEALTH/conditions/04/26/diabetes.genes.ap/index.html
-Steve
http://www.thegenesherpa.blogspot.com
Steve: Family history’s great but only for those people who have access to it. I barely know a thing about anyone in my extended family let alone their medical history and I suspect most people are the same.
Oh, and for chronic conditions like type 2 diabetes, it’s almost impossible for observers to know if someone is affected because there are no visible signs. Constructing an accurate family pedigree of type 2 diabetes is pretty difficult also because many people will remain undiagnosed and/or subclinical for most of their lifetime.
Hsien,
The CGC works with the proband for weeks, if not months refining this tool. Revisiting it with every change. Does that happen now in most centers? No. Should it? Yes.
This is precisely why we need genetic counselors and clinical geneticists. What we are creating is a dynamic family history that changes with continuity of care over TIME
Does it happen in mine? Absolutely.
-Steve
http://www.thegenesherpa.blogspot.com
Steve: Are there any direct DNA testing services that you think are fine? I have considered the HFE one for hemochromatosis for example. I have no symptoms other than achy joints and I would never bother a doctor with it. But I might check on my own…
Do you have an email address?
-Steve
http://www.thegenesherpa.blogspot.com
Wow. Quite a dialogue going here!
Barry: Actually I agree with you – I don’t want people to waste money on genetic tests that won’t help them, either. It’s all about useful testing, for the right people, through the right venue.
At DNA Direct, I strive to present detailed information about test results, risk, current research and preventive measures — BEFORE people purchase a test. As a prelude to the purchase process, there’s an interactive questionnaire the provides response about appropriateness of testing, just in case people don’t read the rest of the site. I’d love your feedback, too, on whether we’ve adequately addressed your concerns.
(To clarify “feedback” since Steve misunderstood — I’m always looking for readers reactions to our content — whether patient, health wonk, clinician, etc. What I care about is not just that we provide accurate info, but that how people READ and understand it is also accurate. All too often, medical-speak is accurate but misunderstood by laypeople, and that can be very dangerous.)
Everyone might be interested in knowing that all DNA Direct’s website and individual, Personalized Reports that testers receive undergo a minimum 3-step clinical review process: a subject matter (in this case of the deCODE test, an MD diabetes expert and physician educator), our clinical director (CGC) and our medical director (MD, PhD geneticist). In the case of deCODE, because it is a new area without medical guidelines, we also worked with deCODE’s clinical team and medical advisors to really dig into the research in addition to our own experts and advisors.
At the end of the day, I guess I fall in line with Hsien’s perspective. We all have to take responsibility. As healthcare consumers, we are agents who should make educated decisions. As healthcare providers, it’s imperative that we provide sound, ethical services. I chose to work for DNA Direct because of the diligence with which the people and company were approaching this new model of providing genetic counseling, education and testing services. (See my interview with Hsien’s for more, or DNA Direct’s Standards & Guideline for Company and Consumers)
On Hemochromatosis: DNA Direct provides counseling and testing for HFE. See here. Let me know if you don’t find the info you need
Also, the Iron Disorders Institute has great resources.
Steve: regarding P values and the DPP trial (NEJM 2006), see the researchers conclusions: “Finally, we did not detect significant interactions between genotypes at either SNP and the DPP interventions. The absence of an effect may not be surprising, since these interventions succeeded primarily by improving insulin sensitivity and these variants affect insulin secretion. However, we did not observe any effect of genotype at these loci in the lifestyle-intervention group, raising the possibility that a behavioral intervention can mitigate the risk conferred by genetic background.” Looking at the graphs in the article gives a pretty strong visual for this argument. All the clinicians I’ve spoken with concur with this interpretation.
Lisa,
Thanks for the information. I reviewed the article and several of the cited sources. As for the graphics: Graphs can be made to look stronger than they are, that is why the gold standard for statistical significance is the p-value. Often the lay public and journalists look at the pretty graphs. With a non-significant evaluation, it would be foolhardy to conclude anything and hope it to stand up in a jury trial.
In addition the Department of Endocrinology at Yale University School of Medicine does not hold the same opinion as the clinicians that you may have spoken with.
Genetic testing is a complex issue, as is all of healthcare. In the end genetic testing will be just fine. GINA will get passed and no one will be at risk for discrimination. But I hope we don’t miss a bunch of iron overload, or diabetes because we rely on a false sense of security because fo a test.
It’s my job as an MD to eval the science and apply it clinically, not the patients’…for now.
-Steve
http://www.thegenesherpa.blogspot.com
Lastly,
In the article: “However, we did not observe any effect of genotype at these loci in the lifestyle-intervention group, raising the ‘possibility’ that a behavioral intervention can mitigate the risk conferred by genetic background.”
The “possibility” is not strong enough to state it as fact. But luckily in this case exercise and diet is not as risky as a drug eluting stent or Vioxx……..
-Steve
http://www.thegenesherpa.blogspot.com
Last one I promise.
The TCF7L2 is involved in signalling and may very well represent what we call a developmental predisposition. The family of proteins it plays a role in is Wnt signalling. This is involved in the development of the gut. It is fishy to raise the possibilty without mentioning that the damage could have already been done in utero. Similar predisposition may be involved with COPD (emphysema).
From NEJM Volume 355:306-308 July 20, 2006 Number 3
“Does this new genetic information have any practical health implications? At first glance, TCF7L2 is not the most attractive of drug targets, since it is closely involved in fundamental developmental processes. The main effect of the high-risk single-nucleotide polymorphisms in relation to diabetes may be developmental and may not be amenable to therapeutic manipulation in the adult patient.”
Do you see how confusing the data is? I sure do.
The jury’s still out. At least in my mind.
-Steve
http://www.thegenesherpa.blogspot.com
Once again DeCODE has found another “region”. Which was also found in Ottawa. It looks promising. But it is not a gene…yet. What will the DTC companies do now?
-Steve
http://www.thegenesherpa.blogspot.com