Association between seven single nucleotide polymorphisms involved in inflammation and proteolysis and abdominal aortic aneurysm

Saratzis, Athanasios; Bown, Matthew J.; Wild, Ben; Nightingale, Peter; Smith, J. P.; Johnson, Christopher; Melas, Nikolaos; Kitas, George D.

doi:10.1016/j.jvs.2013.11.099

Cited by 29 publications

(40 citation statements)

References 51 publications

(83 reference statements)

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“…Further meta-analyses of gene-association studies have identified positive associations for the following SNPs: MMP-3 rs3025058,33 MMP-2 rs243865,34 MMP-13 rs2252070,34 elastin rs2071307,34 C reactive protein rs3091244,35TGF β rs764522 and rs1036095 36. A recent meta-analysis (in press) from our group has not confirmed previously identified putative associations for the ACE inhibitors rs3025058, MMP-3 rs3025058, nitric oxide synthase rs1799752 and methylenetetrahydrofolate reductase rs1801133 SNPs 37. Finally, Jones et al 38 analysed 44 blood lipid- and coronary artery disease-associated loci in a discovery cohort from New Zealand.…”

Section: Genetic Studiescontrasting

confidence: 53%

The genetic basis for aortic aneurysmal disease

Saratzis

Bown

2014

Heart

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Aortic aneurysms are an important cause of cardiovascular death in elderly patients. At present, little is known of the pathobiology of aneurysmal disease and this limits the ability to develop non-surgical treatments to stabilise aneurysms. Both thoracic and abdominal aortic aneurysms (AAA) demonstrate a strong genetic component in their aetiology. Determination of the genetic variants associated with aneurysmal disease is one approach to increasing the understanding the pathways leading to aneurysmal degeneration of the aorta. In this review, we aim to summarise the current knowledge of the genetics underlying the two most common disease phenotypes, thoracic aortic aneurysm (TAA) and AAA. Genetically, AAA represent a multifactorial disease, with the likelihood that there are multiple variants of very low effect sizes contributing to the overall genetic disease risk. Non-syndromic TAA appears to be associated with a smaller number of risk loci with higher individual effect sizes at these loci. Candidate gene and genome-wide approaches have identified robust associations between AAA and variants in/nearby the SORT1, low-density lipoprotein receptor, DAB2IP, LRP1, ELN, CRP, TGFB and various matrix metallo-proteinase genes suggesting that aberrations of lipid metabolism and proteolytic pathways are the key contributors to disease. Some of these associations (eg, LRP1) are not associated with atherosclerosis, suggesting pathways unique to AAA. Genetic variants associated with non-syndromic TAA (ACTA2 and MYH11) are related to the TGFβ pathway, strongly implicated in syndromic TAA, thus suggesting a common pathway between syndromic and non-syndromic TAA.

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Section: Genetic Studiescontrasting

confidence: 53%

The genetic basis for aortic aneurysmal disease

Saratzis

Bown

2014

Heart

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“…Another one, published the same year, which was investigated several genes in AAA presented the similar results for MMP-3 rs3025058 [116].…”

Section: Mmp-3mentioning

confidence: 56%

Overview of MMP Biology and Gene Associations in Human Diseases

Djurić¹,

Živković²

2017

The Role of Matrix Metalloproteinase in Human Body Pathologies

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Interactions of cell with the extracellular matrix (ECM) are crucial for normal development and functioning of the human organism. By regulating ECM integrity and composition matrix metalloproteinases (MMPs) play the main role in ECM molecules signaling and influence processes such as proliferation, migration, differentiation and apoptosis.ECM remodeling is a highly regulated process. When imbalanced it could contribute to pathophysiology of many diseases. The MMPs actions and activity are regulated through different mechanisms such as regulation of transcription, activation of latent MMPs, inhibition of MMP function by tissue inhibitors of metalloproteinases. MMPs are a family of calcium-and zinc-dependent endoproteinase, which share similar structural domains, but differs in substrate specificity, cell localizations and inducibility. Genetic variations in MMPs have been associated with a number of diseases, still not all findings are reproducible. Nine of 23 human genes encoding MMPs are located in a cluster on chromosome 11, which implicate their haplotype-driven effects. They could be important mediators of disease severity and could trigger acute events. In this chapter, we will review the basics of MMP biology and the most significant associations of MMPs variations with cardiovascular and neurological diseases in humans and MMPs therapeutic potential through synthetic inhibitors.

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“…This was tried to be explained by studies on genes effecting the chemokine receptors with important role in the inflammatory process and on gene deletions that play a role in oxidative stress such as endothelial nitric oxide synthase (eNOS) and by many other pathogenetic studies (7). There are also more recent studies on the roles of inflammation and proteolytic process in the pathophysiology and epidemiology of AAA (21)(22)(23). AAA was found to be ten times more frequent in the first-degree relatives of patients with AAA.…”

Section: Discussionmentioning

confidence: 99%

Multi-Drug Resistance-1 [Mdr1, P-gp, Abcb1] Gene Polymorphism in Patients with Abdominal Aortic Aneurysm and Their Family Members

Yağmur¹,

Tekın²

2018

Akd Med J

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Objective: The aim of this study was to investigate the relationship between the 3435C>T polymorphism in the multi-drug resistance-1 gene [MDR1, P-gp, ABCB1] and the development of abdominal aortic aneurysm (AAA). Material and Methods: This study included 75 patients with AAA (Group I), 75 individuals who were first-degree relatives of these patients but did not have AAA diagnosis (Group II), and 75 healthy volunteers whose abdominal aortic diameters were in the normal range (Group III). Genomic DNAs of these individuals were obtained from the peripheral blood. The MDR1:c.3435C>T polymorphism [CC (Wild Type), CT (Heterozygous) and TT (Homozygous) genotypes] was investigated by using the real-time polymerase chain reaction technique (real-time PCR). Results: MDR1 TT genotype was significantly more frequent in Groups I and II compared to Group III (33.3% and 38.6% vs. 8%, respectively, p<0.001). MDR1 CT genotype was also more frequent in Group I and Group II in comparison with Group III (44% and 42.6% vs 25.3%, respectively, p<0.01). Conclusion: The presence of an association between the MDR1 gene polymorphism and the development of AAA suggests that this gene may trigger the pathological mechanisms that play a role in the development of AAA. Additionally, patients with AAA and their first-degree relatives possess similar genetic characteristics in terms of the MDR1 gene polymorphism. Therefore, MDR1 gene polymorphism may be a risk factor for AAA in individuals with a positive family history of AAA.

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Association between seven single nucleotide polymorphisms involved in inflammation and proteolysis and abdominal aortic aneurysm

Abstract: The SNPs included in this analysis were not associated with AAA presence in either study population. However, meta-analysis of the currently available data disclosed a positive association for MMP-3 rs3025058 and MTHFR rs1801133.

Cited by 29 publications

References 51 publications

The genetic basis for aortic aneurysmal disease

The genetic basis for aortic aneurysmal disease

Overview of MMP Biology and Gene Associations in Human Diseases

Multi-Drug Resistance-1 [Mdr1, P-gp, Abcb1] Gene Polymorphism in Patients with Abdominal Aortic Aneurysm and Their Family Members

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