A comparison of genetic chromosomal loci for intracranial, thoracic aortic,
and abdominal aortic aneurysms in search of
common genetic risk factors
Ynte M. Ruigrok
, Rim Elias
, Cisca Wijmenga
, GabriJl J.E. Rinkel
Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands
Complex Genetics Section, Department of Biomedical Genetics, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands
Received 12 November 2006; received in revised form 2 May 2007; accepted 5 June 2007
Background: Genetic factors are likely to be involved in the pathogenesis of intracranial, ascending thoracic aorta, and infrarenal aortic
abdominal aneurysms. Common genetic risk factors for these three types of aneurysms have been suggested. This review describes the results
of whole-genome linkage studies on intracranial, thoracic aorta, and aortic abdominal aneurysms, and compares the genomic loci identified in
these studies in search of possible common genetic risk factors for the three aneurysmal types. Methods: A literature search of all whole-
genome linkage studies performed on intracranial, thoracic aorta, and aortic abdominal aneurysms was performed. The genomic loci
identified in these studies were described and compared in search of similarities between them. Results: Five chromosomal regions on 3p24–
25, 4q32–34, 5q, 11q24, and 19q that may play a role in the pathogenesis of two or more aneurysmal types were identified: 3p24–25 for
thoracic aorta and intracranial aneurysms; 4q32–34 for aortic abdominal and intracranial aneurysms; 5q for thoracic aorta and intracranial
aneurysms; 11q24 for thoracic aorta, aortic abdominal, and intracranial aneurysms; and 19q for aortic abdominal and intracranial aneurysms.
Conclusions: Five chromosomal regions that may include common genetic factors for intracranial, thoracic aorta, and aortic abdominal
aneurysms were identified. Further studies are needed to explore these chromosomal regions in different aneurysm patient groups and may
further help to unravel the disease pathogenesis of aneurysms in general. D 2008 Elsevier Inc. All rights reserved.
Keywords: Aneurysm; Genetic risk factor; Pathogenesis
Dilatation of arteries may lead to aneurysm formation.
Most aneurysms develop on intracranial arteries and the
aorta. Intracranial aneurysms (IA) are characteristically
saccular shaped (i.e., localized outpocketings of the arterial
wall) occurring at arterial branching points  (Fig. 1A).
Aortic aneurysms are mostly fusiform, characterized by
circumferential widening of the artery . Most aortic
aneurysms are found on the ascending thoracic aorta
[thoracic aortic aneurysms (TAA)] and the infrarenal
abdominal aorta [abdominal aortic aneurysms (AAA)] .
The ascending aorta is the section between the aortic root
and the arch (Fig. 1B). TAA located at the ascending aorta
will eventually lead to dissection of the ascending aorta if
left untreated. Thus, TAA and dissections of the ascending
aorta are related conditions. AAA are located below the
renal arteries, and about half of AAA cases extend to the
common iliac arteries  (Fig. 1C).
IA are found in 2% of the general population , and the
incidence of IA rupture leading to subarachnoid hemorrhage
(SAH) is 8 per 100,000 person-years . Most patients with
1054-8807/08/$ – see front matter D 2008 Elsevier Inc. All rights reserved.
Y.M. Ruigrok was supported by The Netherlands Organization for
Scientific Research (project no. 940-37-023).
4 Corresponding author. Department of Neurology, Rudolf Magnus
Institute of Neuroscience, University Medical Center Utrecht, PO Box
85500, 3508 GA Utrecht, The Netherlands. Tel.: +31 30 2508600; fax: +31
E-mail address: firstname.lastname@example.org (Y.M. Ruigrok).
Cardiovascular Pathology 17 (2008) 40 – 47