Exploring the genetic basis of VWD

A Q&A with Paula James (Canada)

A genome-wide association study strategy for von Willebrand Disease (VWD) could yield an exponential increase in knowledge over the next several years, according to Dr. Paula James of the Department of Medicine, Queen’s University (Canada). The Hemophilia World Congress is the “exact, perfect forum” for researchers to develop strategies on this scale, she says.

Q: Where do things stand with genetic testing for bleeding disorders?
A: “Genetic testing is useful and beneficial for patients with hemophilia. With VWD in particular, we still have a lot to learn, and I don’t think genetic testing is useful in every case. It needs to be applied rationally. A genome-wide association study strategy would really help us understand genetic determinants of bleeding outside the obvious places, in the factor VIII or IX gene for hemophilia, or the von Willebrand factor (VWF) gene for VWD.

Q: What’s the difference between hemophilia and VWD in terms of genetic testing?
“Genetic testing is a lot more straightforward for hemophilia, because it is a much more straightforward disorder from a genetic perspective. There’s one gene [the factor VIII gene], one protein, there’s usually a mutation in that gene, and it isn’t more complicated than that. VWD is milder for most people, and you don’t always find clear, pathological mutations in the VWF gene.

“There’s some emerging evidence that we’re not looking at the right genes, that there may be other genetic loci involved in causing the disease. The strength of a genome-wide association strategy is that it tells you where to look, and often it is places you might not think of. The research will take years, and it will be costly. But the technology is available, and a number of other groups of investigators have used this strategy for other diseases, like diabetes and multiple sclerosis. There has been one large publication on more than 30,000 normal people that looked at the genetic control of clotting factor levels, but we’re just starting to put together large populations of patients with bleeding disorders.

“From that number, you get a sense that you need huge sample sizes. So it will take a coordinated, international effort, with people sharing and pooling samples and resources, for us to have the right patient population to actually try and use this strategy effectively.”

Q: Is there any precedent for that level of co-operation?
A: “On this level, I don’t think so. But one of the issues, particularly if we’re talking about hemophilia, is that it’s rare, so to do studies that actually have the numbers, you have to co-operate. That has happened before, but to a much lesser degree. One of the great things about the World Federation meeting is that it’s the exact, perfect forum for us to discuss this with our colleagues. There really isn’t another meeting where we could do this properly.”

Q: If you can get your hands on it, what do you expect to get out of this kind of data?
A: “We are really excited about this. We’ve learned so much in the last 30 years and made so much progress, but it really feels to me like the amount we’re going to learn in the next few years will be exponential. Once again, it’s actually quite straightforward for hemophilia—not to say it’s easy, but there is one gene and that’s where you’re going to look…For milder bleeding disorders, it really is a lot more complicated, so the work is quite exciting.”

Dr. James chaired the session on the Applications of Genetics, held at the XXIX International Congress of the World Federation of Hemophilia, Buenos Aires, Argentina, July 10-14, 2010. Other speakers included Johannes Oldenburg (Germany) and Jorge DiPaola (U.S.A.). Their state of the art paper, published in a special supplement of the WFH’s official journal Haemophilia, is available here.

Last Updated September 2010