Early-onset type 1 diabetes may have less to do with certain genes causing inborn genetic errors, and more to do with normal genes behaving differently for those with the disease.

To find out how certain twins get diabetes while the other does not, Stanford University scientists studied two types of mice models: Non-obese diabetic (NOD) mice with the gene variants that closely resembles a predisposing gene complex in humans (MHC), and another group of non-diabetic mice without the predisposing genes. The group found that clusters of genes were consistently expressed in the NOD mice in specific tissues at certain times. What is even more interesting is the gene expression "signatures" occurred before certain signs of diabetes were noticed, such as hyperglycemia.

So if these pre-diabetes clues can be identified in humans, then warnings and preventive therapies can be developed to help people way before the onset of disease.

Enlarged hearts are found often, but not exclusively, in those who are obese, have diabetes or high blood pressure. People with none of these underlying problems can be affected, as can elite athletes.  For example, a post-mortem diagnosed the problem in Cameroon football midfielder Marc-Vivien Foe, who died in 2003 after collapsing during an international match in France. Elite runner Olympic hopeful Ryan Shay died of complications involving an enlarged heart - the very condition that made him a great runner.

An international  research team headed up by Imperial College, UK say they have for the first time linked enlarged hearts with a gene, osteoglycin (Ogn).

Work carried out on rodents and some 30 humans indicated that Ogn - which has never before been linked with heart function - regulated the growth of the heart’s main pumping chamber, its left ventricle.  When this gene behaves abnormally the heart can become enlarged, putting the person at an increased risk of common heart diseases and heart attacks.

For further information, click on:

http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/newssummary/news_29-4-2008-13-31-10

Elaine Warburton  www.geneticsandhealth.com

Scientists from Imperial College London and other international institutions have discovered a gene sequence that is associated with a 2cm expansion in waist circumference, a 2kg gain in weight, and a tendency to become resistant to insulin, which can lead to type 2 diabetes. The sequence is found in 50% of the UK population.

The study shows that the sequence is a third more common in those with Indian Asian than in those with European ancestry. This could provide a possible genetic explanation for the particularly high levels of obesity and insulin resistance in Indian Asians, who make up 25% of the world’s population, but who are expected to account for 40% of global cardiovascular disease by 2020.

The new gene sequence sits close to a gene called MC4R (Melancortin-4 Receptor), which regulates energy levels in the body by influencing how much we eat and how much energy we expend or conserve. The researchers believe the sequence is involved in controlling the MC4R gene, which has also been implicated in rare forms of extreme childhood obesity.

Elaine Warburton  www.geneticsandhealth.com
 

G&H’s INTERVIEW WITH NAVIGENICS

Navigenics approached Genetics and Health for an interview. With so much written about similar genomics companies such as 23andme, Knome, deCODE genetics, I was intrigued to learn more about this company.  In particular, Navigenics appears to be the only company within this industry genre who provides a comprehensive wellness model – a healthcare model that Opaldia, the genetic screening and health surveillance company I founded, endorsed whole-heartedly. 

I interviewed Navigenics’ Medical Director Dr Michael A Nierenberg MD, clinical professor of medicine, emeritus at Stanford University to find out what makes Navigenics stand out amongst its competition.  He was most candid in his responses and the company has been open and transparent in responding to my follow-up queries, for which I am most grateful. 

The following article takes an in-depth look into Navigenics’ genomic services including how the company has positioned its services in relation to its ‘competition’ but importantly how Navigenics answers some of the ethical issues surrounding the whole field of genomic testing. The article has been divided into the following sections:

Navigenics #1 - ”My genes, my health, my life – who are Navigenics?”

Navigenics #2 - ”A stroll through your genomic park – about the test”

Navigenics #3 - ”SNP testing – can it be used for disease risk assessment?”

Navigenics #4 - ”Low penetrance v high pentrance genes”

Navigenics #5 - ”Corporate or pragmatic genomics”

Navigenics #6 - ”Privacy, insurance, GINA and ethics”

Navigenics #7 - ”The barriers to success!”

Navigenics #1 -  ”My genes, my health, my life – who are Navigenics? 

The much anticipated launch! 

April 8^th, 2008 Navigenics Inc launches its genomics service In New York. 

It has branded its service as “Navigenics Health Compass”.  

In its launch literature the company writes: “Navigenics aims to transform medicine from a ‘sick care’ model of ‘wait and see’ to the emergence of early risk detection.  It aims to empower individuals with opportunity and knowledge and to take preventative steps and a hands on approach to their family’s health and wellness” 

Navigenics – a veritable who’s who in genetics and business 

Navigenics has some highly influential supporters including Kleiner, Perkins, Caulfield and Byers (KP) and Sequoia Capital who have recently invested just under US$4m.   Amongst its heavy hitting Board members, co-founders and partners are David Brailer, until recently the Bush Administration’s point man on electronic health records and more recently Chairman of Health Evolution Partners, a private equity fund that invests in healthcare.   

Company co-founders are Dietrich Stephan, a Director at the Translational Genomics Research Institute and David Agus, a protein biomarker researcher at Cedars-Sinai Medical Hospital in LA.  Navigenics CEO Mari Baker was KPs ‘executive in residence’ and is former President of BabyCenter a website for parents. 

Also advising is politically connected Greg Simon, now President of Michael Milken’s FasterCures organization and previously Al Gore’s chief domestic policy advisor. 

Navigenics has close ties to Affymetrix and uses Affy’s gene chip (23andme uses Illumina’s chip).  Affy’s former associate general counsel Stephen Moore is now Navigenic’s general counsel and the company’s VP Business development, Sean George was also at Affy.  Amy duRoss, Navigenics Head of Policy and Business Affairs, was formerly with the Californian Institute of Regenerative Medicine and is also Navigenics’ spokeswoman.

Navigenics #2 - A stroll through your genomic park – about the test

The Navigenics service 

When you sign up to the Navigenics service you effectively enrol as a member and not as a patient or customer.   For US$2,500 you subscribe to an annual package which includes a genomic scan to identify your lifetime risk (compared to an average American male or female) of developing 18 core, treatable diseases such as heart disease, Alzheimer’s and type II diabetes.  Included in the package is on-line and telephone support from experienced genetic counselors who will hand-hold you throughout the process and be available to discuss your results in ‘easy to understand’ language.   

Over time, Navigenics will be adding additional information and tests to its core service portfolio.  As a subscriber to the service, you will have access and be advised of any updates and how they relate specifically to your health risk profile.  Ongoing annual subscription for the Navigenics service will be at a nominal annual subscription, currently US$250 pa. After subscribing you will receive a saliva collection kit.  Once you have provided a saliva sample you will be asked to send the kit back to Navigenics’ CLIA certified lab in California, where your DNA will be extracted and scanned. 

About a month later, you will be informed of your test results via your own personal account within a secure area of Navigenics’s website.  The results also come with an explanation of what they mean and the impact they may have on your overall health risk profile.  In addition there will be guidance and recommendations on how to mitigate against any identified health risk through your personalized health action plan. 

For example, if you are a female, your profile may contain the following results: 

Alzheimer’s              Yourself  8%            Average population   17%

Breast cancer          Yourself 14%           Average population   13% 

This is interpreted as you are at lower risk of developing Alzheimer’s during your life compared to the average female but at higher risk of developing breast cancer during your life than an average female.  Regular screening for breast abnormalities may well be a sound investment for your ongoing wellness.   Dr Nierenberg comments “Navigenics wishes to foster an ongoing partnership and relationship between members and the medical communities.  This is achieved through an educational program and repeated contact. The genetic screen only provides part of the health picture so our members need to be counseled on the fact that as there is also a large environmental component involved in disease development, so they may never get it.” Genetic counseling and having adequate access to this service is of paramount importance to Navigenics.  Elissa Levin, heads up the company’s genetic counseling services.  Dr Nierenberg describes the counseling team. “The counseling team provides members with clinically based knowledge to promote a greater understanding of their health risks, to decrease anxiety at every step of the way and to encourage them to take positive steps to live as long and healthy a life as possible.” 

Navigenics #3 - SNP testing – can it be used for disease risk assessment?

Navigenics has focused on around 100 of the most definitive research papers on SNPs (single nucleotide polymorphisms) that have been most strongly associated with 18 particular diseases such as breast cancer, type II diabetes, cardiovascular disease.  The company has built an algorithm (mathematical computer program) that estimates the risk of a healthy person developing a disease if their genome has the relevant SNP. 

The company has spent immense time and financial resources on engaging its panel of scientific and clinical experts to analyze the many hundreds of SNP association studies.  Says Dr Nierenberg:  

“It is a pre-requisite for Navigenics that any SNP to be included within its core panel must have undergone rigorous scientific and clinical evaluation and had the supporting research replicated in an appropriately peer reviewed paper. Functional data and magnitude of effect are also taken into account, but studies are not automatically excluded if functional data is unavailable or the effect estimate is small.  That being said, there is currently nothing on our panel with a relative risk less than 1.1 of developing a disease if the associated SNP is carried.”

99% of human DNA sequences are the same across the entire human population.  However, variations in DNA sequence can have a major impact on how humans respond to disease, the environment and drugs & medicines. SNPs are DNA sequences that occur when a single nucleotide (A,T,C or G) in the genome sequence is altered.  For example - AAGCT to ATGCT.  For a variation to be considered a SNP, it must occur in more than 1% of the population.  Many SNPs have no effect on cell function, but many could predispose people to disease or influence their response to a drug.     

A single altered gene is only part of the disease development equation.  To be more at risk of developing a complex disease such as cardiovascular disease, an individual needs to possess a number of interactive SNP ‘faults’ in multiple genes.    A SNP that is common in one geographical region or ethnic group, may be much rarer in another.  This is one of the main arguments against using SNP based analysis for the whole population.  For example if much of the research has been carried out on a predominantly ‘pure’ Caucasian cohort the test for that particular SNP may only be appropriate for a Caucasian and not, for example an African or Asian. Navigenics SNP data is largely Caucasian, but the company is more versant in the actual calculations of life-time risk and who was included in that which may well include non-Caucasians.  Dr Nierenberg explains:  

“We have reason to believe that the data applies across ethnic groups, but further data is needed to confirm this, will be collected over time, and reported to our members. For now we are very transparent about the groups in which the studies are done, whether Caucasian or in some cases non-Caucasians. Where associations have been looked for in other ethnic groups, generally we see that the effect sizes are consistent across other ethnicities including African Americans and Asians.”

As there are estimated to be over 3 million SNPs there is obviously an infinite amount of research still to be carried out on SNPs and their interaction both at the genomic and environmental levels.  The SNP single gene model is probably too simplistic to be able to provide risk scores for complex diseases, so I asked Dr Nierenberg how Navigenics foresaw their product evolving in the future. 

Dr Nierenberg advised: “We’re not basing our entire approach per se on the test, rather we’re looking at promoting wellness and the effects of the environment on health.  We believe our members should be pointed in the right direction in terms of their genetic predisposition to disease and offered suggestions on how to manage their risk.” 

In terms of the future evolution of the product, Dr Nierenberg advises that the results of ongoing studies will be added to the core test to enhance Navigenics’ service offering.

Navigenics #4 - Low penetrance v high pentrance genes

SNPs are known as ‘low penetrance genes’ where it will only sometimes produce the symptom or trait with which it has been associated at a detectable level. In this case of low penetrance it is difficult to distinguish environmental from genetic factors.   

Whereas ‘high penetrance genes’ such as the breast cancer genes BRCA 1 and 2 are those where the trait will almost always be shown by the individual carrying the faulty gene. In this case a BRCA 1 and 2 carrier will have over an 80% chance of developing breast and/or ovarian cancer in their lifetime. 

Most high penetrance genes have been patented, in the case of BRCA 1 and 2 by Myriad Inc. It is a costly process to obtain a license from the patent owner and in the case of BRCA 1 and 2 the cost of a Myriad test is around the US $5,000 mark, two to five times more expensive than genomic screens and therefore probably prohibitive to genomic screening companies, in cost terms.   

Dr Nierenberg advises that Navigenics have made a conscious decision not to include high penetrance genes in their core panel, preferring to focus on those low penetrance genes that are affected by environmental factors.  

“In the case of the BRCA genes, only a relatively small proportion of the population – as low as 5% - carry one or more of these genes.  We are focused on SNPs that are apparent within whole populations. We make it clear in our literature that we do not test for this type of gene.”

Navigenics #5 - Corporate or pragmatic genomics

Navigenics uses Affymetrix’s gene chip which is able to test around 1 million genetic markers.  However Navigenics has initially focused on 18 specific, treatable diseases which form the foundation of its designated SNP panel.  This panel will expand over time.   

I asked the question of what happened to a member’s DNA – whether it was disposed of or stored.  Dr Nierenberg explained that a member’s DNA was stored in anticipation of future advances in understanding how genes and the environment interact in disease development.  

“As part of a member’s subscription, we will automatically advise them of these advances if relevant to their particular disease risk as and when they become available”. 

The phrases “corporate genomics” and “the Microsoft of the genome” have been coined to describe the genomic business models of companies such as Navigenics, 23andMe and deCODE Genetics where getting access to your genome would require handing it over to a company that assumes it knows better that you do which parts of your genome you are entitled to see, and then charge you again and again for updated versions of the same product.  

However, the counter argument is that from modern medicine’s inception, we have effectively handed over our health to a specialist body – physicians, who themselves have grown into corporate organisations – hospitals, who, in turn are empowered to make clinical and financial judgements on our health and well-being.  Is there really a tangible difference? 

Dr Nierenberg defends Navigenics business model by citing the very arguments that are causing deep rifts within the genetics communities, namely, Navigenics only provides members with test results for diseases where firstly there is sufficient research on the SNPs in terms of robustness of testing, clinical utility and outcomes, and secondly, but importantly, the diseases they focus on are those where something can be done to reduce the risk of developing that disease - such as exercise, nutrition and regular screening.   

Imagine the confusion and furore if Navigenics were to provide its members with their full 1 million marker analysis!  Navigenics’ (and others) sensible, if somewhat patriarchal approach of ‘drip feeding’ results to members as and when the research is robust enough to bring the SNP into the public domain, is one that should be applauded not derided.  Yes, they and others have the potential to make substantial profits if consumers chose the service.  But the corporate world is also littered with the carcasses of companies that didn’t get it right.

Navigenics #6 - Privacy, insurance, GINA and ethics

One of the main consumer concerns is that of privacy of information, both in terms that a genetic test has been undertaken but also that the results of the test are kept private and out of the public domain.  At the time of writing, the controversial GINA (Genetic Information Non-discrimination Act) is being passed by the US Senate which will enable genetic testing information to be kept private and not be used to discriminate against an individual, particularly by the insurance industry.  The insurance industry is understandable against the Bill. 

Dr Nierenberg advises that Navigenics takes the whole issue of security of data very seriously.   

“Navigenics takes precautions such as multiple servers, encryption and security audits … each member has access to their own section of the website which is password protected.  However, if a member forgets their password, there is a highly complicated route to get back in.  It is not just a case of emailing the password to an email address. … GINA legislation will be helpful in terms of protecting sensitive information”. 

The company has also incorporated a rigorous Ethics Advisory Board tasked to develop policies and report to the Executive Board in the fields of bioethics, patient rights, health information technology and technology and data security. In terms of working with the health insurance industry, Dr Nierenberg advises that at present the service Navigenics offers is ‘direct to consumer’ and the health insurance industry are not be involved.  However the company is already working with health insurers to integrate this type of testing and service as part of a standard medical insurance package. He says: 

“There is a strong health economic argument to incorporate genomic screening into an insurance package.  Catching a disease early or even preventing it must surely be in everyone’s best interests rather than wait until the disease is established and expensive treatment is almost certainly needed”. Dr Nierenberg uses the example of HIV testing and the insurance industry to describe how he believes genetic testing will evolve over time   “… Back in the 1980’s HIV testing was hated and received a lot of abuse.  However, over time the test has become familiar and everyone is comfortable with routine HIV testing”. Dr Nierenberg says Navigenics is also looking to expand it results service to become fully consumer friendly.  They are working on communication with its members via cell phone and other internet options.  However none of these initiatives can be implemented until the company is satisfied that data can be securely anonymized. 

Navigenics, at some stage, may well request permission to use a member’s DNA in anonymized research studies.  This will bring up a wealth of ethical issues such as informed consent at every stage of the research and explanation for what research the DNA will be used for.

Navigenics #7 - The barriers to success!

When founding my old company Opaldia, probably the single most challenging aspect of early adoption of genetic testing was physician barriers.  Mostly this was borne out of a genuine lack of understanding about the field of genetics but also concerns that testing was too much in its infancy and tests had not been subject to rigorous clinical evaluation.  Time and again the phrase ‘not undergone prospective trials’ was used as a defense against bringing genetic testing into mainstream medical practice. 

I was interested to learn how Navigenics proposed to overcome this barrier.  Dr Nierenberg explained that Navigenics has developed a physician education program. He says: 

“We’re developing our own on-line material but we’re working with Medscape to develop a CME program for physicians to access.  The educational material will cover a large range of information from basic to complex”. 

Dr Nierenberg describes the word genetics as a ‘hot button’, guaranteed to evoke the strongest of reactions.  He is philosophical about the fact that genetics research and genetic advances are still at a relatively embryonic stage but made the analogy with the completeness of research into the effects of smoking. 

“Everyone is aware that smoking is not good for health. Would it be of benefit to continue smoking until all the research evidence to prove smoking is bad for you is complete?  … This is the same for genetics…. If there is a means to identify an individual’s increased risk of developing a disease then isn’t it is everyone’s best interests to use this?” 

There have been a number of recent articles on the state of play of personalized genomics, some of which have been less than complimentary to industry players.  The term ‘recreational genomics’ has been used to describe these services.  I asked Dr Nierenberg whether he considered any damage had been done to this embryonic field by these articles.  Dr Nierenberg again took a philosophical view on these articles:  “Navigenics is no way a ‘recreational’ genomics company and does not wish to contemplate entering any ‘recreational’ field. It is a company focusing on the wellness and prevention aspects of health.  Our service focuses on actionable entities and things of substance such as cardiac disease, not eye colour or such like. We welcome regulation and make heavy use of genetic counseling.  We follow all NHGC latest guidelines and best practice and more …” Dr Nierenberg and his team believe that the company is ‘… ahead of the curve and when you are leading a new field there is always a level of scepticism about your service and an expectation that you will be challenged every step of the way’. He cited the example of the C-Reactive Protein (CRP) test and its use in diagnosing cardiac inflammation.  Initially the test was ridiculed but now it is established as a routine diagnostic test used alongside CT heart scanning – another modality which initially received poor press.   

Navigenics firmly believes that through educating both clinicians and the public, it will only be a matter of time before genomic screening become part of routine health and wellness programs.  By focusing its services around a serious health delivery model rather than a ‘recreational’ model, Navigenics anticipates achieving its company vision to transform medicine from a ‘sick care’ model of ‘wait and see’ to the emergence of early risk detection and prevention of disease development.

I hope you enjoyed this series of articles about Navigenics’ Wellness Services.  I am most thankful to Dr Michael Nierenberg and the Navigenics’ team for the opportunity to discuss in-depth the issues surrounding the whole field of personal genomics services, wellness and health management.

Elaine Warburton  www.geneticsandhealth.com

Many gene studies focus on WHICH genes cause a person’s risk of developing a disease (forward genetics) but few focus on HOW those genes can lead to disease.  Researchers at Merck and Co, deCODE genetics and academic centres in the US and France have focused on the latter and shed light on the complexity of common disease causes where multiple genetic changes are involved (functional genetics).

Two studies analysed DNA variations, patterns of gene expression in disease tissue, and clinical data on a large scale to identify which gene networks linked to metabolic disorders (a range of symptoms that are thought to cause obesity, diabetes and atherosclerosis or heart disease).

The first study on mouse livers looked at finding genes that might be linked to obesity, diabetes and heart disease.  The researchers created gene networks and located highly connected sub-networks of core genes that were known to be linked to obesity, diabetes and heart disease. They also identified, and validated at the experimental level, three new genes thought to cause obesity: Lpl, Pmp1l and Lactb.

The second study on over 1,000 human blood and fat tissue samples from Iceland, and using data from the first study, created a gene expression network of human obesity traits.  This human obesity network showed considerable overlap with the mouse network.

The researchers concluded that:

“A core network module in humans and mice was identified that is enriched for genes involved in the inflammatory and immune response and has been found to be causally associated to obesity-related traits.”

The next question is WHY?

Elaine Warburton  www.geneticsandhealth.com

Our early human ancestors originated from a hot, humid climate where natural selection focused on dispersing heat.  As humans migrated to colder climates there would have been evolutionary pressure to adapt to their new settings by boosting the processes that produce and retain heat.

Genes involved in energy metabolism are therefore likely to be central to heat and cold tolerance. 

Researchers from the Dept of Human Genetics, University of Chicago, USA tested this theory by genotyping 873 tag SNPs in these ‘cold tolerance’ genes in 54 worldwide populations and found a correlation with climatic variations.

Among the results were strongest signals from several SNPs, that had previously been associated with body evolution directly related to cold tolerance.

One, a leptin receptor,  LEPR R109K, which is integral in appetite regulation and energy balance, was the source of one of the strongest signals of evolutionary selection. One version of this gene is common in locations with colder winters. This allele is additionally correlated with the increased capability to absorb oxygen and expel carbon dioxide, which happens when the body produces heat. The same genetic variation has also been linked to a lower BMI, a smaller amount of abdominal fat, and a lower blood pressure. This specific leptin receptor, therefore, is protective against metabolic syndrome.

However, not all of the genes related to tolerance of colder climates protects against the metabolic syndrome. For example, an increased blood glucose level might protect the body from cold weather by making energy more readily available for production of heat. However, this also raises the risk of type 2 diabetes. FABP2 A54T was a gene that was more prevalent in populations with lower temperatures actually increases BMA, promotes storage of fat in the body and increases levels of cholesterol. While this protects the body against the cold, it increases the risk of heart disease and diabetes, and thus metabolic syndrome.

Variation in climate may be correlated with other aspects of environmental variation. Nevertheless, the results are consistent with the idea that climate has been an important selective pressure acting on candidate genes for common metabolic disorders such as obesity, diabetes and heart disease.

Thousands of years later we live in an era that combines widespread central heating with an overabundant food supply, so those genetic alterations which protected us from cold have taken on a different sort of significance. They alter our susceptibility to a whole new set of diseases, such as obesity, coronary artery disease and type 2 diabetes.

For further information, please click on:

http://genetics.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pgen.0040032&ct=1

Elaine Warburton  www.geneticsandhealth.com

Early embryos yield stem cells,(photo courtesy of BBC news www.bbc.co.uk/news) 

The Uk’s fertility regulator Human Fertilisation and Embryology Authority (HFEA) has given the green light to two teams of scientists for the creation of hybrid human-animal embryos.

Scientists, research institutions and patient groups have challenged the UK government for much of the last year: the Department of Health wanted to prevent the creation of human-animal hybrid embryos - which would be used to create stem cells for medical research - but scientists argued it would slow down crucial work into treatments for diseases including Alzheimer’s, Parkinson’s and diabetes. Reason eventually triumphed and the government has now backed down.

Scientists from King’s College London and Newcastle University will now be able to carry out research using the embryos, which they hope will pave the way for new treatments for a range of diseases and conditions including diabetes.

Director of Research at Diabetes UK, Dr Iain Frame says of this highly sensitive issue:
“Diabetes UK has made a public commitment to supporting research using human embryos … However, given the pace and complexity of this area of medical research, it is also committed to reviewing its policy on this sensitive issue on a regular basis. … What is at issue here is not the possibility that science will create new forms of hybrid creatures. The law is already very clear that embryos created for the purpose of stem cell research will be destroyed.”

“Nevertheless, the question of hybrid embryos does raise ethical questions that are different in substance from those raised in previous consultations on stem cell research. The charity therefore welcomes further consultation on the question and will be consulting its stakeholders in due course.” Elaine Warburton

Researchers at the Albert Einstein College of Medicine of Yeshiva University, in New York, claim they have found the genes responsible for storing fat in cells.  They have identified the FIT1 and FIT2 (Fat-Inducing Transcripts 1 and 2) genes that package fat in the form of lipid droplets.  Storing fat in lipid droplets is important for enabling cells to use fat as an energy source ….  but having high amounts of these droplets leads to obesity.

Obesity is a major cause of Type 2 diabetes, which is becoming a world epidemic. The discovery of genes that influence the development of obesity could help allow scientists and physicians to understand why some people gain weight more than others.

The study’s findings could open up a wealth of new avenues to understand and treat obesity and obesity-related conditions such as Type 2 diabetes.

Elaine Warburton

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.