Dataset Information

Association analysis of genetic polymorphisms of factor V, factor VII and fibrinogen ? chain genes with human abdominal aortic aneurysm.

ABSTRACT: Increased activity of the coagulation system is associated with the increased risk of many arterial thrombotic diseases and atherosclerosis. The purpose of this study was to evaluate the influence of selected polymorphisms in genes coding for coagulation factor V (1691 G/A, the so-called Leiden mutation), factor VII (-323 0/10 bp insertion/deletion) and fibrinogen ? chain (-455 G/A) on the risk of abdominal aortic aneurysm, a particular form of atherothrombosis. We conducted a case-control study of 153 Polish patients hospitalized due to abdominal aortic aneurysm (AAA) and compared the results to those obtained from matched healthy control subjects. The polymorphisms were ascertained through genotyping by polymerase chain reaction and restriction digestion of amplified fragments. The study revealed that individuals carrying heterozygous genotype GA for the fibrinogen ? chain -455 G/A mutation had at least a 2-fold greater likelihood of AAA development compared to control subjects (OR=3.01; 95% CI 1.83-4.96). The cases possessing homozygous mutant genotype (AA) had no significant risk of developing AAA compared to the control subjects (OR=1.12; 95% CI 0.33-2.44; p=0.83). Concerning factor V 1691 G/A and factor VII -323 0/10 bp mutations, we did not find any statistically significant correlation between them and AAA occurrence. In conclusion, we suggest that the -455G/A polymorphism of the fibrinogen ? chain gene is a potential genetic marker to identify the risk of AAA.

SUBMITTER: Oszajca K

PROVIDER: S-EPMC3503697 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Association analysis of genetic polymorphisms of factor V, factor VII and fibrinogen β chain genes with human abdominal aortic aneurysm.

Oszajca Katarzyna K Wroński Konrad K Janiszewska Grażyna G Bieńkiewicz Małgorzata M Panek Michał M Bartkowiak Jacek J Szemraj Janusz J

Experimental and therapeutic medicine 20120612 3

Increased activity of the coagulation system is associated with the increased risk of many arterial thrombotic diseases and atherosclerosis. The purpose of this study was to evaluate the influence of selected polymorphisms in genes coding for coagulation factor V (1691 G/A, the so-called Leiden mutation), factor VII (-323 0/10 bp insertion/deletion) and fibrinogen β chain (-455 G/A) on the risk of abdominal aortic aneurysm, a particular form of atherothrombosis. We conducted a case-control study ...[more]

PMID: 23181128

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Project description:Background:Abdominal aortic aneurysm (AAA) is the full thickness dilation of the abdominal aorta. However, few effective medical therapies are available. Thus, elucidating the molecular mechanism of AAA pathogenesis and exploring the potential molecular target of medical therapies for AAA is of vital importance. Methods:Three expression datasets (GSE7084, GSE47472 and GSE57691) were downloaded from the Gene Expression Omnibus (GEO). These datasets were merged and then normalized using the "sva" R package. Differential expressed gene (DEG) analysis and weighted gene co-expression network analysis (WGCNA) were conducted. We compared the co-expression patterns between AAA and normal conditions, and hub genes of each functional module were identified. DEGs were mapped to co-expression network under AAA condition and a DEG co-expression network was generated. Crucial genes were identified using molecular complex detection (MCODE) (a plugin in Cytoscape). Results:In our study, 6 and 10 gene modules were detected for the AAA and normal conditions, respectively, while 143 DEGs were screened. Compared to the normal condition, genes associated with immune response, inflammation and muscle contraction were clustered in three gene modules respectively under the AAA condition; the hub genes of the three modules were MAP4K1, NFIB and HPK1, respectively. A DEG co-expression network with 102 nodes and 303 edges was identified, and a hub gene cluster with 10 genes from the DEG co-expression network was detected. YIPF6, RABGAP1, ANKRD6, GPD1L, PGRMC2, HIGD1A, GMDS, MGP, SLC25A4 and FAM129A were in the cluster. The expression levels of these 10 genes showed potential diagnostic value. Conclusion:Based on WGCNA, we detected 6 modules under the AAA condition and 10 modules in the normal condition. Hub genes of each module and hub gene clusters of the DEG co-expression network were identified. These genes may act as potential targets for medical therapy and diagnostic biomarkers. Further studies are needed to elucidate the detailed biological function of these genes in the pathogenesis of AAA.

Project description:BackgroundAbdominal aortic aneurysms (AAAs) represent a complex multifactorial hemodynamic, thrombotic, and inflammatory process that can ultimately result in aortic rupture and death. Despite improved screening and surgical management of AAAs, the mortality rates have remained high after rupture, and little progress has occurred in the development of nonoperative treatments. Intraluminal thrombus (ILT) is present in most AAAs and might be involved in AAA pathogenesis. The present review examined the latest clinical and experimental evidence for possible involvement of the ILT in AAA growth and rupture.MethodsA literature review was performed after a search of the PubMed database from 2012 to June 2020 using the terms "abdominal aortic aneurysm" and "intraluminal thrombus."ResultsThe structure, composition, and hemodynamics of ILT formation and propagation were reviewed in relation to the hemostatic and proteolytic factors favoring ILT deposition. The potential effects of the ILT on AAA wall degeneration and rupture, including a review of the current controversies regarding the position, thickness, and composition of ILT, are presented. Although initially potentially protective against increased wall stress, increasing evidence has shown that an increased volume and greater age of the ILT have direct detrimental effects on aortic wall integrity, which might predispose to an increased rupture risk.ConclusionsILT does not appear to be an innocent bystander in AAA pathophysiology. However, its exact role remains elusive and controversial. Despite computational evidence of a possible protective role of the ILT in reducing wall stress, increasing evidence has shown that the ILT promotes AAA wall degeneration in humans and in animal models. Further research, with large animal models and with more chronic ILT is crucial for a better understanding of the role of the ILT in AAAs and for the potential development of targeted therapies to slow or halt AAA progression.

Dataset Information

Association analysis of genetic polymorphisms of factor V, factor VII and fibrinogen ? chain genes with human abdominal aortic aneurysm.

Publications

Association analysis of genetic polymorphisms of factor V, factor VII and fibrinogen β chain genes with human abdominal aortic aneurysm.

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