Friday, November 14, 2008

Warfarin DNA Testing Predicted to Save Over One Billion Dollars and Improve Patient Safety

The AEI-Brookings Joint Center for Regulatory Studies released a study in November, Health Care Savings from Personalizing Medicine Using Genetic Testing: The Case of Warfarin that confirms that DNA testing will dramatically improve the safety and effectiveness of Coumadin (warfarin).

Warfarin, brand name Coumadin, is a powerful medicine that saves hundreds of thousands of lives every year. It works by “thinning” the blood and preventing clots that would otherwise cause strokes, heart attacks, or other blood clotting disease. Every year as many as two million Americans start taking warfarin and at any given time there are four or five million on the medicine.

The amount of warfarin required for someone to reach their target INR, the measure of the effectiveness of warfarin, varies as much as forty-fold from person to person. This interpersonal variation in warfarin dose requirement makes it time consuming and dangerous to identify the optimal dose for patients. Dangerous because the therapeutic window, the difference between the effective dose and the toxic dose of warfarin, is exceedingly small. The consequences of warfarin over-dosing are also severe — resulting bruising and bleeding are the second most prevalent cause of emergency room visits and are responsible for thousands of deaths every year. There are some safer, replacement drugs in development, but they are still at least three or four years away from being ready for market.

During the last decade scientists have discovered that most of the individual variation in warfarin dose requirement is due to genetics or variation in the DNA of individual patients. This variation, for which genetic tests are now available at the initiation of warfarin therapy, occurs at two sites on the DNA. The most important, known as CYP2C9, controls the levels of the enzyme that’s responsible for the breakdown and elimination of warfarin. Approximately 35% of the population have variant forms of this enzyme that slow down the elimination of warfarin from the system. Instead of a person reaching their warfarin and INR steady state in four or five days, it can take two weeks or more. Genetic testing is the only reliable way to determine when steady state is reached.

The second most important site of genetic variation affecting warfarin maintenance dose is the vitamin K receptor (VKORC1), the site of action of warfarin. This makes sense as it is well known that vitamin K intake affects the action of warfarin. Genetic variation is common at this site. Ninety percent of Asian-Americans have the "low-dose" variation: meaning they required a lower dose of warfarin, while most African-Americans have the "high-dose" variation requiring more drug to get adequately anticoagulated. Patients of European descent fall somewhere in the middle.

When people have DNA testing there are now computer programs that take into account their genetics, age, sex, weight and other factors, such as amiodarone or other medicines they may be taking to calculate their warfarin dose. This calculated dose is many times more accurate than the dose determined without the DNA testing.

Patients need to be proactive in obtaining this testing. Adoption of the testing by doctors and anticoagulation clinics is slow, despite endorsement by leading scientists, the FDA, and patients who have had the testing and credit it with saving them from the dire consequences of a warfarin overdose. Additionally, uptake has been slow because of the inherent conservatism of the medical establishment and lack-luster interest from pharmaceutical manufacturers.

Widespread adoption of DNA testing to predict warfarin dose will cut down on doctor and emergency room visits and save thousands of lives. A recent Brookings/American Enterprise Institute study estimates that routine use of DNA testing would save the healthcare system as much as $2 Billion per year. It will also help make warfarin therapy more accessible to the millions of people who are not now taking warfarin but who would benefit from it.

Monday, November 10, 2008

DNA & Godfather of Soul

The Godfather of Soul is also a father many times over. In addition to six children of record, three additional children have now been proven to have been fathered by the late soul singer, James Brown. About a dozen DNA tests have been performed since he died in December 2006 of heart failure at the age of 73. Some people have been ruled out as Brown's children, while other tests are still pending.

The emerging offspring are adding even more twists to the legal squabbling that emerged after the Sex Machine's death. The estate disputes between the singer's children already involves as many as two dozen lawyers.

Friday, November 7, 2008

DID YOU KNOW?

It takes about eight hours for one of your cells to completely copy its DNA.

You could fit one million threads of DNA across the period at the end of this sentence.

If you were to start reciting the order of the ATCGs in your DNA tomorrow morning, at a rate of 100 each minute, 57 years would pass before you reached the end (provided that you did not stop to eat, drink, sleep, use the bathroom etc.)

Our genes are remarkably similar to those of other life forms. For example, we share 98% of our genes with chimpanzees, 90% with mice, 85% with zebra fish, 21% with worms, and 7% with a simple bacterium such as E. coli.