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Gene mingling increases sudden death risk
Date:10/12/2009

gene that play a role in the disease.

With collaborators in South Africa, they have focused on a family affected by long-QT syndrome. This extended South African family includes 500 characterized members, 205 of which carry the same long-QT-causing mutation. And as expected, not all of the mutation carriers have symptoms of the disease.

The gene NOS1AP (which codes for a "docking" protein for the enzyme nitric oxide synthase) was identified in a genome wide association study as being a determinant of the QT interval in healthy individuals. George, Schwartz and colleagues examined whether different versions (variants) of the NOS1AP gene impacted the symptoms and QT interval in the South African family.

They found that people who had the primary long-QT-causing mutation and one of two common variants of NOS1AP had a higher probability of cardiac arrest and sudden death than primary mutation carriers who didn't have those NOS1AP variants.

"In this case it appears that variants of NOS1AP somehow predispose those individuals to a worse form of the disease," George said.

The investigators also found that the family members who had the NOS1AP variants had the longest QT intervals in a group of people who all have long QT intervals.

"We're excited that these findings begin to address how to manage patients with long-QT mutations," George said.

"What we're hoping is that NOS1AP genetic testing in mutation carriers who are asymptomatic or minimally symptomatic could tip the balance toward being more aggressive in treating them or perhaps backing off and watching them for a little longer."

George and colleagues will also continue to search for other genetic modifiers, which could add to a "risk equation" to determine the best therapy.

"Individualizing therapy in this disease is really a paradigm for personalized medicine," George said. "What do we need to know to make a treatment decision? Now we're star
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Contact: Leigh MacMillan
leigh.macmillan@vanderbilt.edu
615-322-4747
Vanderbilt University Medical Center
Source:Eurekalert

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