CINCINNATI—With the help of $8 million in federal stimulus funds, University of Cincinnati (UC) researchers will continue their efforts to identify genes responsible for the formation and rupture of intracranial aneurysms.
The funds, spread over two years, are part of a grant renewal from the National Institutes of Health (NIH) in support of the Familial Intracranial Aneurysm (FIA) II study, a collaborative research effort of investigators examining multiple populations in the United States and elsewhere. The grant was made possible by the American Recovery and Reinvestment Act of 2009, an economic stimulus package enacted in February 2009.
The FIA study, with UC as the coordinating center, is examining genetic and other environmental risk factors for intracranial aneurysm. Its first phase, FIA I, was a five-year study involving 27 clinical centers in four countries. In keeping with ARRA requirements, recruitment for FIA II will be limited to the study’s North American sites. Researchers will continue to interface and collaborate with studies and patients in international populations.
Intracranial aneurysms (IA) are “blisters” which form within the arteries of the brain. A rupture of an aneurysm may lead to subarachnoid hemorrhage, which occurs in about 30,000 people annually in the United States with 35 percent dying within the first 30 days. Most of the deaths from subarachnoid hemorrhage are due to rapid and massive brain injury from the initial bleeding, so prevention of aneurysm formation is important.
Identification of susceptible genes in the formation and rupture of intracranial aneurysms would help researchers understand how aneurysms develop and could lead to the development of improved screening, diagnosis and prevention, with corresponding decreases in health care costs.
“This grant is a big shot in the arm for our research,” says Joseph Broderick, MD, chairman of UC’s neurology department and principal investigator for the study. “We’re close to identifying the genes responsible for IA, but we still need to nail them down and the specific reason why they cause the formation of aneurysms.”
Phase I gathered information from 441 families (2,800 subjects) who had multiple members with intracranial aneurysm and gave their consent for participation in the study. Information-gathering included collection of genetic material (via blood samples), extensive interviews and magnetic resonance angiography.
Phase II, Broderick says, will enroll an additional 1,800 subjects with intracranial aneurysm as well as 200 additional families. Genetic and environmental information from these subjects will be compared to controls without aneurysms from other NIH-funded studies in an attempt to replicate earlier findings from this as well as ongoing studies of intracranial aneurysm in other countries.
FIA researchers have observed significant association with intracranial aneurysms for two genes, COL9A1 (type IX collagen) and PDE1A (phosphodiesterase 1A) which they hope to replicate in the next stage of the study. In addition, they have presented data indicating that those genes interact with smoking in such a way that smoking greatly enhances the effect of the genes.
“We’ve already identified that smoking is critical,” says Broderick, “so while we’re waiting to find the exact gene, stopping smoking is still the best way to prevent the formation and rupture of intracranial aneurysms.
“Additionally, high blood pressure is also a known risk factor for aneurysm formation and should be controlled.”