Arterial dilatation leading to aneurysms occurs most commonly in the cerebral arteries (intracranial aneurysm, IA) and the aorta (aorta aneurysm, AA). However, the molecular details of aneurysm formation are poorly understood.
Aneurysms of the aorta can be localised in the thoracic aorta (TAA) and, most frequently, in the abdominal (AAA) aorta. The prevalence of AAA is 5% in men above 50 years of age. In addition to advanced age and male gender, smoking and a family history of AAA are major risk factors. Siblings of AAA patients have an approximately 10-fold increased risk of developing an AAA. Aorta aneurysms (AAs) are considered to be silent killers since they usually remain asymptomatic, but if they do rupture they are often fatal.
We have collected the world’s largest AAA patient cohort from 8 centres in the Netherlands (>1,000 DNA samples). We are currently performing association studies, and use deep-sequencing techniques to identify causal variants. We are also performing linkage analysis in families with a Mendelian inheritance pattern of AA, followed by deep-sequencing of the linkage peaks.
The prevalence of IA is 2% in the general population. A familial predisposition is the strongest risk factor for developing an IA. Rupture of an IA leads to a subarachnoid haemorrhage (SAH), which is a subtype of stroke. Rupture occurs at a young age (40 – 60 years old) and the patient’s prognosis after rupture is poor: 50% die and another 20% become dependent on help for daily activities.
For IA we also have one of the world’s largest cohorts of DNA samples (>800 samples). By combining a genome-wide association study and a genome-wide expression study, we are currently identifying new candidate genes that determine the development of IA and its subsequent rupture. In collaboration with the AAA research group, we are also searching for common genetic risk factors for aneurysms in general.
Contact
for aorta aneurysm (AA) research: Annette F. Baas
email for intracranial aneurysm (IA) research: Ynte M. Ruigrok, PhD
email