DNA Testingby David Mendosa Patient Advocate
The first genetic test available to determine a risk factor for type 2 diabetes recently became available. I just beta tested and discussed it with the company's CEO and several other officials. DNA Direct, a privately funded company in San Francisco, offers the test of this gene that can lead to diabetes.
An Icelandic company named deCode Genetics discovered the gene. DNA Direct has a contractual relationship with deCode.
The name of this gene variant is the transcription factor 7-like 2 gene (TCF7L2), which is too difficult to remember. So it goes by the nickname "deCode T2" or simply "TT."
The test works, so it passed my beta test. You might say, however, that I failed it, because the test show that I am genetically at risk of having diabetes by carrying two copies of the variant.
No big surprise here, because ever since 1994 I've known that I have diabetes. And I don't feel that I failed, because it gave me knowledge about who I am, in the same sense that my genealogical research on my family helped me understand my origin.
If I were planning on raising a family, this knowledge would be even more important. If I were married and if my wife also tested positive for the diabetes gene, we might think twice about having children. When both parents have two copies each of diabetes gene, their children are at a greater risk than when one parent has it.
But there may be a more immediate reason why you would want to know if you, like me, test positive for this gene. I picked up my first hint from Clyde Shores, deCode's vice president for diagnostic marketing and sales when we met at the American Diabetes Association's June scientific sessions in Chicago. All he would say then was that some people have lower response rates to some diabetes drug if they test positive for this gene.
The second hint is on DNA Direct's website. It says there that, "It can also help your doctor to determine the most effective treatment."
Until I talked with DNA Direct's CEO Ryan Phelan and three company officials this week I kept wondering if they had anything specifically in mind. They certainly do. Their studies show that sulfonylureas - perhaps the most common diabetes drug - might not be as effect for people who, like me, are positive for the diabetes T2 gene.
"Some of them do respond to a sulfonylurea," says Lisa Lee, director of content development, "but not as many as respond to metformin or who are negative for the TT gene. They are less likely to be able to reach a normal A1C level from being on a sulfonylurea compared with people who are negative for the gene or on metformin."
If you have type 2 diabetes, you are more likely to test positive for this gene variant than people who don't have type 2. Technically, that means carrying the risk variant for the TCF7L2 gene on both chromosomes. If you don't have this gene at all or even if you have only one copy of it, you don't have this genetic risk of diabetes.
In classical inheritance terms this is means the gene is recessive. However, type 2 diabetes is not a classical genetic disease where a single gene alone determines the outcome. The environment and the interaction of multiple genes determines the outcome. People who have a single T gene do not have a statistically significant higher risk of developing type 2 diabetes than individuals who do not have any T variants.
How much more likely is your risk if you have two copies of the gene variant? The good news is that it's not a sure thing, as it is with some other conditions. About 18 percent of those of us who have type 2 diabetes are positive for the T2 risk marker. Among the general population of Americans those who have both copies of this gene are a whopping 141 percent more likely to develop diabetes.
If you have pre-diabetes, you have different reasons to be tested for the gene than if you already have diabetes. "The good news," Ryan says, "is that people who are pre-diabetic are likely to be able to prevent diabetes with lifestyle or therapeutic intervention. You can help reduce the impact or prevent it."
She says that their studies show that people with pre-diabetes who were carrying the same risk marker as I do did better on intervention with lifestyle and medication than a control group that went on the same lifestyle and intervention program. "They did better because they were carrying the risk marker." That made them more motivated than the people in the control group.
Still, I can understand why some people with a parent who has a genetically-carried disease would be reluctant to find out for sure whether or not they carry that gene - especially if having that gene means that it's going to kill you. For example, the great songwriter and folk musician Woody Guthrie died of a degenerative neurologic affliction, Huntington's disease, as did his mother. Woody's son, Arlo, says he doesn't want to know if that's going to kill him.
But having the diabetes gene is different in a couple of respects. Having this gene doesn't mean for sure that you will get diabetes. And as we well know, diabetes is not a death sentence - if you control it.
In the future DNA Direct expects that they will be able to offer tests for other diabetes genes, Ryan says. "But right now, other than the TCF7L2 gene variant, none the variants that have been discovered to date are significant in terms of clinical utility."
So is it worth your money to get this test? When DNA Direct began offering the test, they had to charge $500 for it, because the laboratories that run the tests for them charge so much.
But they have put pressure on the labs to bring down their prices, so that when I interviewed the DNA Direct people they told me that they had just announced a new price of $300. That includes $240 to the lab and only $60 to DNA Direct for interpreting the results.
The test is a mail-in kit, and unlike all the tests that we are familiar with, uses no blood. You simply squab each cheek with something like a big Q-tip. Whether you have pre-diabetes or diabetes itself, getting testing is easy and worth it.