ABSTRACT
OBJECTIVES: Abdominal aortic aneurysm (AAA) and its complications are among the most serious cardiovascular diseases and its occurrence has risen sharply in recent years. The aim of this pilot study is to explore the relationship between the methylation of matrix metalloproteinases and tissue inhibitors of the metalloproteinases genes' promoter region, and abdominal aortic aneurysm (AAA) through the detection of the methylation status of MMP2, TIMP2, TIMP1, and MMP9 genes in peripheral blood. METHODS: The study included 43 males with verified AAA (case group) and 34 healthy males (control group). The methylation status of the genes' promoter region was detected by methylation-specific polymerase chain reaction (MS-PCR). RESULTS: In adominal aortic aneurysm patients, the methylation ratio of MMP2 gene was positive in 9.3 % (4 cases), 2.3 % (1 case) had methylated TIMP2 gene, 7.0 % (3 cases) had methylated TIMP1 gene, while the methylation ratio of MMP9 gene was positive in 93.0 % (40 cases). In the control group, MMP2 gene was found to be methylated in 5.9 % (2 cases), 5.9 % of cases had methylated TIMP2 and TIMP1 genes (2 cases), and MMP9 gene was found to be methylated in 91.2 % (31 cases). CONCLUSION: In our pilot study, we found no association between DNA methylation of gelatinases and their tissue inhibitors, and the development of an abdominal aortic aneurysm (Tab. 2, Fig. 1, Ref. 27).
Subject(s)
Aortic Aneurysm, Abdominal , DNA Methylation , Matrix Metalloproteinase 2 , Matrix Metalloproteinase 9 , Tissue Inhibitor of Metalloproteinase-1 , Tissue Inhibitor of Metalloproteinase-2 , Aortic Aneurysm, Abdominal/genetics , Humans , Male , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , Matrix Metalloproteinases , Pilot Projects , Tissue Inhibitor of Metalloproteinase-1/genetics , Tissue Inhibitor of Metalloproteinase-1/metabolism , Tissue Inhibitor of Metalloproteinase-2/genetics , Tissue Inhibitor of Metalloproteinase-2/metabolismABSTRACT
Interleukin-18 (IL-18), pro-inflammatory cytokine, plays important role in antitumor immunity. Polymorphisms in the IL-18 gene may lead to its altered production/activity and such modulate susceptibility to prostate cancer. The aim of this study was to evaluate the relationship between the -607 and +105 polymorphisms in the IL-18 gene and the risk of prostate cancer development and progression in Slovak population. The study was performed using 425 patients with prostate cancer, 270 patients with benign prostatic hyperplasia (BHP) and 263 healthy male controls. The statistically significant association of the -607 AC genotype (OR = 2.24; p < 0.001), CC genotype (OR = 1.86; p = 0.006), as well as C allele (OR = 1.27; p = 0.033) with the higher risk of prostate cancer development was observed. No association of the IL-18 -607 polymorphism and BHP was detected. The subset analysis revealed the significant association of the -607 AC genotype (OR = 2.01; p = 0.008) with development of higher-grade carcinomas (Gleason score ≥7) and the strong association of the -607 AC genotype (OR = 3.11; p < 0.001), CC genotype (OR = 2.96; p < 0.001) as well as C allele (OR = 1.51; p = 0.003) with the higher risk of prostate cancer development in the group of patients with PSA < 10 ng/ml. The -607 AC genotype was also connected with significantly higher IL-18 plasma concentrations. No association between the IL-18 +105 polymorphism and prostate cancer was observed. The analysis of the distribution of the -607 and +105 haplotypes showed significant association of the - 607 C/ + 105 A and - 607 C/ + 105 C haplotypes with the risk of prostate cancer. This study found that the IL-18 -607 promoter polymorphism could contribute to prostate cancer development in Slovak population. Its presence was also associated with development of higher-grade carcinomas and therefore may influences the prognosis and aggressiveness of the disease.
