genotyping for hemophilia

Hemophilia Genotyping for All

Genotyping will play a key role in clinical care
Author: Connie Miller, PhD, and J. Michael Soucie, PhD

Learn more in this issue's cover article, "What's Your Genotype?"

When the factor VIII and factor IX genes were cloned and sequenced 25 years ago, there was great anticipation of the impact those events would have on hemophilia care. While the goal of safe and effective treatment products through DNA technology has been realized, use of the individual’s genetic information for family testing and personalized care has been more difficult because of the number and complexity of the mutations causing hemophilia.

As technology has advanced and more patients have been genotyped worldwide, it has become clear that knowledge of genotype will play a key role in clinical care. Genotyping can allow clinicians to predict inhibitor risk and the need to ­target gene therapy and other innovative treatments by mutation type. (See cover story, “What’s Your Genotype?”)

Inhibitors are the number one blood safety issue for people with hemophilia today. The development of an inhibitor often results in more difficult and costly care. In order to adequately assess the inhibitor risk for a new product, we must know both the expected baseline rate of inhibitors and all the risk factors for inhibitor development. This information can best be learned through surveillance of an at-risk population.

To learn more about inhibitors and the reasons they develop, the Centers for Disease Control and Prevention (CDC) is conducting a study of inhibitors as part of its surveillance program called the Universal Data Collection (UDC) System. People with hemophilia at certain treatment centers around the country are eligible to join the study, which involves keeping close track of their infusions and providing a blood specimen for inhibitor testing at least once per year. Participants also are genotyped at the CDC. Results are provided to their physician.

More than 800 people have been enrolled in the CDC’s inhibitor study and genotyped. While this is only a small portion of the people with hemophilia in the US, this project demonstrates the feasibility of current genotyping strategies and the value of both genotyping and prospective surveillance for inhibitors in better understanding who gets inhibitors and why, and then developing effective inhibitor prevention.

The National Hemophilia Foundation’s planned initiative to genotype the community could lead to the day when all people with hemophilia in the US know their genotype. Participation in this initiative benefits both the individual and the bleeding disorders community. You can find bleeding disorders data on the CDC’s Web site.

Connie Miller, PhD J. Michael Soucie, PhDConnie Miller, PhD, is a research biologist and J. Michael Soucie, PhD, is associate director for science, at the Centers for Disease ­Control and Prevention in Atlanta.