Background: There is growing evidence that genetic variants have an impact on the pathogenesis of intracranial aneurysm (IA). Recently, the genetic locus around the elastin gene (7q11) has been identified as linked to IA in a Japanese population. Our aim was to confirm these results in Caucasian populations. Methods: We conducted a case-control study in 120 Caucasian patients with IA and 172 controls to investigate 8 single nucleotide polymorphisms (SNPs) and various haplotypes within the elastin gene, which were frequently found and associated with the phenotype in the Japanese populations. Real-time PCR and melting curve analysis were used for the detection of genotypes. Results: Allele frequencies and genotypes were equally distributed between Caucasian cases and controls. We failed to identify haplotypes that are associated with the phenotype in our population, which is in contrast to the Japanese study. However, allele frequencies in control populations differ between Caucasians and Japanese. Conclusions: We found no association between SNPs and haplotypes of the elastin gene and the occurrence of IA in our Caucasian populations. However, our data provide strong evidence for racial/ethnic differences in the association of SNP and specific haplotypes of the elastin gene with the phenotype. There might be other genetic variants of the elastin gene associated with IA in Caucasians. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Background: Vascular remodeling generated by reactive oxygen species contributes to aneurysm formation. The NADPH oxidase system is a major source of superoxide anion not only in phagocytes, but also in endothelial and vascular smooth muscle cells. Polymorphisms of p22phox, an essential component of the NADPH oxidase system, are found to be associated with atherosclerosis, while a recent study found a significant association between the 214C>T polymorphism and the occurrence of ischemic cerebrovascular disease. We conducted a case-control study to investigate the relationship of five polymorphisms of the p22phox gene and the occurrence of cerebral aneurysms. Methods: The study population consisted of 113 patients with intracranial aneurysms and 53 control subjects. The 214C>T polymorphism was investigated by restriction fragment length polymorphism analysis, while polymorphisms 381T>C, 480G>A, 521C>T, and *24A>G were analyzed by direct sequencing of exon 6 and adjacent intronic sequences. Results: The analysis of a primary study sample comprising 35 cases and 28 controls failed to show a significant association between any of the five polymorphisms and the occurrence of intracranial aneurysms using both allele frequencies and genotypes (all nominal p > 0.05). Although there was a deviation from Hardy-Weinberg equilibrium in cases at the 521C>T locus (nominal p < 0.05), this could not be confirmed in a second study sample of 78 patients. Haplotypes were constructed regarding three frequent polymorphisms (214C>T, 521C>T, and *24A>G); haplotype frequencies in cases and controls were not significantly different. Conclusion: Although polymorphisms of the p22phox gene located in the coding region and the 3′-untranslated region were reported to be associated with atherosclerosis and cerebrovascular disease, our data provide evidence that there is no association between these polymorphisms and the occurrence of cerebral aneurysms in Caucasians. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

No description available.

Incidence of abdominal aortic aneurysm (AAA) is increasing in the aging society of the western world. Development of AAA is mostly asymptomatic and is characterized by a bulge in the abdominal aorta. However, AAA may suddenly rupture, which results in an internal bleeding associated with a high mortality rate. Patients with AAA undergo regular screening until treatment indication. To date, statistical criteria are used to decide whether the risk of rupture exceeds the risk of intervention. Models of AAA development help to understand the disease progression and to yield patient-specific criterion for AAA rupture. Up to date, sophisticated models of AAA development exist. These models assume the abdominal aorta as a thin-walled structure, which saves the computational effort. This thesis aims at investigating the importance of employing a thick-walled model of the aorta. The effects on AAA development that cannot be captured with a thin-walled model are of interest. In Paper A, the thick-walled model of growth and remodeling of one layer of a AAA slice has been extended to a two-layered model. The parameter study has been performed to investigate the influence of mechanical properties and growth and remodeling (G&amp;R) parameters of two individual layers on the gross mechanical response and G&amp;R of the artery. It was concluded that the adventitia acts to protect the arterial wall against rupture even in pathological state. In Paper B, the model was extended to an organ level model of AAA development. Furthermore, the model was incorporated into a so-called Fluid-Solid-Growth (FSG) framework, where the AAA development is loosely coupled to the blood flow conditions such as wall shear stress. One patient-specific geometry of the abdominal aorta is used to illustrate the model capabilities. A transmurally non-uniform distribution of the strains of individual arterial constituents was observed. In addition, an increased aneurysm tortuosity was observed in comparison to a thin-walled approach. These findings signify the importance of a thick-walled approach to model the aneurysm development. Finally, the proposed methodology provides a realistic basis to further explore the growth and remodeling of AAA on a patient-specific basis. / <p>QC 20140311</p>

Diss. (sammanfattning) Uppsala : Univ., 2002. / Härtill 5 uppsatser.

Diss. (sammanfattning) Linköping : Linköpings universitet, 2005. / Härtill 4 uppsatser.

Thesis (M.S.)--University of Michigan, 1982. / eContent provider-neutral record in process. Description based on print version record.

Thesis (M.S.)--University of Michigan, 1982. / eContent provider-neutral record in process. Description based on print version record.

Thesis (Ph. D.)--University of Houston, 2005. / Includes bibliographical references (leaves 100-110). Also available online (PDF file) by a subscription to the set or by purchasing the individual file.

Thesis (Ph. D.)--University of Houston, 2005. / Includes bibliographical references (leaves 100-110).