The aim of the study was to investigate the effect of functional polymorphisms in promoters of the MMP-2 (-1306 C > T), MMP-3 (-1171 5A > 6A), MMP-9 (-1562 C > T), MMP-12 (-82 A > G), TIMP-1 (-372 C > T), and PAI-1 (-675 4G > 5G and -847 A > G) genes on the growth rate of small abdominal aortic aneurysms.
MMP9rs2234681 microsatellite was the only genetic determinant of TE/A in AAA patients (P = .003), followed by hypercholesterolemia and antiplatelet use.
We also assessed the potential association between 2 functional single nucleotide polymorphisms in the genes MMP9 (-1561C/T; rs3918242) and MMP13 (-77A/G; rs2252070), and the presence of large AAAs.
Analyses identified MMP-9 p-2502 single nucleotide polymorphism (odds ratio [OR], 0.54; 95% confidence interval [CI], 0.31-0.94; P = .029) as a significant confound discriminating between control vs slow-growth AAA, MMP-9D165N (OR, 0.49; 95% CI, 0.26-0.95; P = .035) and LRP1 (OR, 4.99; 95% CI, 1.13-22.1; P = .034) between control vs aggressive-growth AAAs, and methyltetrahydrofolate reductase (OR, 2.99; 95% CI, 1.01-8.86; P = .048), MMP-9 p-2502 (OR, 2.19; 95% CI, 1.05-4.58; P = .037), and LRP1 (OR, 4.96; 95% CI, 1.03-23.9; P = .046) as the statistically significant confounds distinguishing slow-growth AAAs vs aggressive-growth AAAs.
No associations with AAA were identified for other SNPs assessed in this study including rs1799750 (MMP1), rs3918242 (MMP9), rs486055 (MMP10), rs2276109 (MMP12), rs2252070 (MMP13), rs4898 (TIMP1) or rs9619311 (TIMP3).
The combined approach of direct experimental confirmation of the functional alterations of MMP-9 SNPs and logistic-regression analysis revealed significant association between MMP-9 genotype and abdominal aortic aneurysm.
This study provides further evidence to support the role of MMP-9 in the pathogenesis of AAA, and indicates that the MMP9 C-1562T functional polymorphism may represent a genetic component contributing to susceptibility to this vascular disease.
A recently published genome wide association study of abdominal aortic aneurysms (AAA), based on pooled case control data of European ancestry, identified four new loci for AAA: SMYD2 (top single nucleotide polymorphism [SNP] rs1795061), LINC00540 (rs9316871), PCIF1/MMP9/ZNF335 (rs3827066), and ERG (rs2836411).
It is noteworthy that contrary to a previous study, we did not find an association between the MMP9 (nt-1562) polymorphism and AAA, suggesting genetic heterogeneity of the disease.
This study examines the associations of the SEPP1, SELENOS, TXNRD1, TXNRD2, GPX4, and SOD2 polymorphisms and selenoprotein P (SeP) and thioredoxin concentrations with the development of abdominal aortic aneurysm (AAA) and aortoiliac occlusive disease (AOID), as well as their influence on cardiac phenotype.
Two recent GWAS have identified genetic markers associated with an increased risk of AAA located within the genes for DAB2 interacting protein (DAB2IP) and low density lipoprotein receptor-related protein 1 (LRP1).
An increasing body of evidence demonstrates that genetic factors, including 3p12.3, DAB2IP, LDLr, LRP1, matrix metalloproteinase (MMP)-3, TGFBR2, and SORT1 loci, are associated with AAA development.
To examine the role of polymorphisms in angiotensin converting enzyme (ACE, I/D) and angiotensin II receptor (AT1R, A1166C) in the development of abdominal aortic aneurysm (AAA).
Treatment with OPG had no inhibitory effect on AAA development in the angiotensin II model in ApoE‑/‑ mice, which developed suprarenal aneurysms, although it increased vessel wall thickness of the aorta and total collagen in C57Bl/6J mice using the CaCl2 model that induced infrarenal dilation of the aorta.
The aortic walls of patients with abdominal aortic aneurysms (AAA) and of healthy controls were examined for elastin, collagen I and III, and the intermediate filament proteins desmin and vimentin by immunohistochemical, enzyme histochemical, and routine histological techniques.
Therefore, polymorphisms of ELN, estrogen receptor alpha (ERalpha) and beta (ERbeta), progesterone receptor (PR) and TGFbeta1 genes and their products may be involved in the abdominal aortic aneurysm (AAA) development.
After infusion of angiotensin II (Ang II) for 4 weeks and β-aminopropionitrile (BAPN) for 2 weeks, 58% of C57/6J wild-type (WT) mice developed AAA associated with enhanced expression of IL-18; however, disease incidence was significantly lower in IL-18<sup>-/-</sup> mice than in WT mice (p < 0.01), although no significant difference was found in systolic blood pressure between WT mice and IL-18<sup>-/-</sup> mice in this model.