University of Utah. US: In an unprecedented international study, researchers from Europe and
the United States have shown that individuals carrying a particular
genetic variant in the PHACTR1 gene are at reduced risk of sustaining
cervical artery dissection, a major cause of stroke in young and
middle-aged adults.
Cervical artery dissection is caused by a tear in an artery supplying
the brain (carotid or vertebral) that can lead to blood clotting within
the artery, potentially causing occlusion of downstream vessels and
brain infarction (stroke). The disease is relatively uncommon in the
general population, but it is an important cause of stroke in people
under 50.
Researchers in the international CADISP (Cervical Artery Dissections
and Ischemic Stroke Patients) consortium wanted to identify genes that
predisposed people to cervical artery dissection, so they screened the
entire genome of 1,400 patients with the disease and 14,400 patients
without it. The results of their research were published online in Nature Genetics (www.nature.com/ng/) on Nov. 24, 2014.
“Understanding the mechanisms by which this region of the genome
appears to influence key vascular functions could have major
applications for the treatment of these severe and disabling
conditions,” says study co-author Jennifer Majersik, M.D., associate professor of neurology at the University of Utah School of Medicine and director of the University of Utah Stroke Center. “More research is clearly needed to nail down the underlying mechanisms.”
Minor neck trauma such as lifting weights or sustaining whiplash
injury in a roller-coaster, recent infection, migraine, and hypertension
are predisposing factors for cervical artery dissection, but the
underlying mechanisms are largely unknown and many times no risk factors
or precipitating traumas can be found. Several lines of evidence
suggest that genetic risk factors could contribute to the occurrence of
the disease. Investigating the genes influencing the risk of cervical
artery dissection is important to better understand its mechanisms and
improve prevention strategies.
Cervical artery dissection is one of the most common causes of stroke
in younger patients seen at University of Utah Health Care. In 2009-10,
when this international study was beginning, Majersik contacted nearly
100 patients previously treated for dissection by physicians in the
University of Utah Stroke Center. Forty of them responded and came back
to the Clinical Neurosciences Center to have their blood drawn for this
important genetic study.
“I am grateful that so many of our patients were willing to come back
to our center to assist in this study, says Majersik, who is a member
of the International Stroke Genetic Consortium. “I think many of them
were motivated by the desire to contribute to their neurologist’s
understanding of the disease and a hope that that knowledge would
improve the lives of their family and community members,”
With them, she is now participating in another similar international
collaboration – this time to determine the genetic determinants of
cerebral venous thrombosis, another common cause of stroke in the young.
“It is only through these large international consortia that questions
such as these—the genetics of rare but devastating forms of stroke—can
be answered,” Majersik says.