Hypermethylation of p16 tumor-suppressor gene in ameloblastic carcinoma, ameloblastoma, and dental follicles.

PURPOSE: The high rate of p16 gene alterations in malignant neoplasms suggests the important effect of this tumor-suppressor gene mutation on the malignant behavior of tumoral lesions. The present study investigated the possible methylation of the p16 tumor in ameloblastic carcinoma, ameloblastoma, and dental follicles. MATERIALS AND METHODS: Eighteen samples of ameloblastic carcinoma, ameloblastoma, and dental follicles of mandibular impacted third molar were selected from available documents in the archives of the Department of Oral and Maxillofacial Pathology, Taleghani Hospital and the Department of Oral and Maxillofacial Pathology, Shahid Beheshti University of Medical Sciences, Tehran, Iran. After confirming the initial diagnosis, 6-µm sections were used for DNA extraction. A CpG island methylation of p16 was identified by polymerase chain reaction. RESULTS: Although CpG methylation of p16 was observed in all ameloblastic carcinoma samples, only 1 ameloblastoma specimen exhibited the mutation. The mutation was not detected in other ameloblastoma specimens or in any dental follicle sample. CONCLUSIONS: The p16 alteration might play a role in the malignant progression of ameloblastic carcinoma. It is worth mentioning that ameloblastoma can be further differentiated from ameloblastic carcinoma based on molecular observations.

C-reactive protein (CRP) gene polymorphisms: implication in CRP plasma levels and susceptibility to acute myocardial infarction.

C-reactive protein (CRP) is one of the many molecular factors involved in pathogenesis of coronary artery disease which its plasma levels are associated with increased risk of cardiovascular events. The present study designed to determine whether polymorphisms in the CRP gene are associated with plasma CRP levels and susceptibility to acute myocardial infarction (AMI). Plasma CRP levels were measured in patients with AMI and control subjects and genomic DNA and peripheral blood mononuclear cells (PBMCs) were extracted. The -717A/G and 1059G/C CRP polymorphisms were detected. The mRNA expression of CRP gene and plasma levels of CRP and interleukin-6 (IL-6) were also analyzed. The -717A/G variation was significantly associated with higher CRP levels, but 1059G/C variation was associated with lower CRP levels. The AA genotype frequency of -717A/G variation was significantly more frequent in the patients than control subjects. By contrast, the genotype and allele distribution in 1059G/C of patient were not statistically different between patients and controls. There were significant differences in circulating levels of CRP and IL-6 in the patients than in controls. The mRNA expression levels of CRP were significantly higher in the patient plasma compared with controls. Our results indicate relationship between many polymorphisms in CRP gene and risk of AMI which suggest that genetic variations in CRP might be helpful for determining susceptibility to AMI in Iranian patients. In addition, CRP gene polymorphisms are associated with plasma CRP levels and susceptibility to AMI might be related to CRP gene expression which affects its plasma levels.

Evaluation of PKM2 and MAPK8IP2 Polymorphism in Ameloblastic Carcinoma: A Retrospective Quantitative Study.

Ameloblastic carcinoma (AC) is a rare malignant epithelial odontogenic tumor that histologically retains the features of ameloblastic differentiation and exhibits cytological features of malignancy in the primary or recurrent tumor. It may develop within a preexisting ameloblastoma or arise de novo or from an odontogenic cyst. Epidemiological evidence shows that human cancer is generally caused by genotoxic factors, genes involved in the susceptibility of cancer, including those involved in metabolism or detoxification of genotoxic environment and those controlling DNA replication. Nowadays, gene polymorphism has an important role in development of malignant tumor. We report a case series study of ameloblastic carcinoma and ameloblastoma to show the role of PKM2 and MAPK8IP2 polymorphisms in these tumors. The DNA was extracted separately from specimens in paraffin sections of the tumor. Polymorphism of these genes was determined by PCR-RFLP (Polymerase Chain Reaction-Restriction fragment length polymorphism) method. The allele distributions of all samples were in Hardy-Weinberg equilibrium. The genotype and allele distribution in these genes were not statistically different between patients and controls.

Genetic polymorphism of interleukin-6 gene and susceptibility to acute myocardial infarction.

OBJECTIVES: Inflammatory processes play a pivotal role in the pathogenesis of atherosclerosis. Genes coding for cytokines such as interleukin-6 (IL-6) are candidates for predisposing to the risk of coronary artery disease. The aim of this study was to investigate whether molecular polymorphism of the IL-6 gene is involved in the predisposition to acute myocardial infarction (AMI). METHODS: Genomic DNA and peripheral blood mononuclear cells of patients with AMI and controls were extracted. IL-6 gene variations were evaluated by polymerase chain reaction followed by restriction enzyme analysis. The mRNA expression of IL-6 gene and plasma levels of IL-6 and C-reactive protein (CRP) were analyzed. RESULTS: The prevalence of 'C' allele in -174 G/C variation was higher in patients with AMI than in controls. The IL-6 -174 'C' allele is associated with high levels of IL-6 in the patients, of which the patients with CC and GC genotypes significantly have higher IL-6 concentrations, respectively. Increased CRP concentrations were associated with -174 G/C variation in the patients compared with controls. The mRNA expression levels of IL-6 were significantly higher in the patient compared with controls (P<0.001). CONCLUSION: The findings of this study indicate the relationship between IL-6 gene polymorphism and the risk of AMI, which suggests that genetic polymorphism in IL-6 gene, might be helpful for determining susceptibility to AMI in Iranian patients. In addition, susceptibility to AMI might be related to IL-6 gene expression, which affects its plasma levels. CRP plasma levels also were associated with IL-6 gene variation in the patients.

Tumor necrosis factor-α: investigation of gene polymorphism and regulation of TACE-TNF-α system in patients with acute myocardial infarction.

A polymorphism within tumor necrosis factor-α (TNF-α) gene promoter and contribution of TNF-α converting enzyme (TACE) have been reported to be associated with TNF-α production which may increase susceptibility to heart failure such as acute myocardial infarction (AMI). However, the relationship between this polymorphism and susceptibility to AMI and the mechanism of TACE-TNF-α system regulation has poorly been studied. Genomic DNA and peripheral blood mononuclear cells (PBMCs) of patients with AMI and control subjects was extracted. The -308 G/A TNF-α polymorphism was detected. The mRNA transcription and protein expression levels of TNF-α and TACE were analyzed by real time RT-PCR and flow cytometry respectively as well as plasma TNF-α by ELISA. The 'A' allele frequency of TNF-α was significantly more frequent in the patients than controls (P < 0.001). There were statistically significant differences in TNF-α and TACE mRNA and protein levels as well as circulating TNF-α in the patients. However, these levels were higher in the patients who carry 'A' allele. There were significant positive correlation between these mRNAs and protein expression levels (r = 0.66, P < 0.001, r = 0.78, P < 0.001 respectively). These data suggest that genetic polymorphism in TNF-α might be helpful for determining susceptibility to AMI in Iranian patients. The TACE-TNF-α system in circulating leucocytes is stimulated which these results demonstrate that in patients with AMI, TACE expression in PBMC increases with TNF-α expression and processing of TNF-α in PBMC might be regulated by TACE at transcriptional, translational, and post-translational levels in AMI.

Pathogenic mechanisms in varicose vein disease: the role of hypoxia and inflammation.

AIMS: Although the aetiology of varicose veins remains unknown, recent studies have focused on endothelial cell integrity and function. Among the regulatory factors of vessel tone, synthesises, pro- and anti-inflammatory, adhesion molecules and the transcription factor hypoxia inducible factor-1 alpha (HIF-1alpha), which are responsible for recruiting leukocytes, are very important. METHODS: Investigation in this study focused on the expression of ICAM-1, E-selectin and HIF-1alpha on endothelial cells using immunostaining and RT-PCR in varicose vein specimens compared with controls. RESULTS: Findings of this study showed alterations of the intima, such as focal intimal discontinuity and denudation of endothelium in varicose veins. Based on data derived from immunostaining and RT-PCR, no major differences were identified between ICAM-1 and E-selectin expression in varicose vein specimens compared with controls. In contrast, immunostaining results identified HIF-1alpha expression in five (5/20) varicose vein specimens, whereas no control saphenous vein specimens expressed HIF-1alpha. CONCLUSIONS: These findings could explain other evidence of hypoxia in varicose veins. Finally, results already obtained in this investigation suggest that the process of pathogenesis of varicose veins is not restricted to the role of adhesion molecules.

Genetic polymorphisms and plasma levels of matrix metalloproteinases and their relationships with developing acute myocardial infarction.

OBJECTIVES: Matrix metalloproteinases (MMPs) play an important role in early atherosclerosis, plaque rupture, extracellular matrix remodeling, and myocardial infarction (MI). MMP gene polymorphisms contribute to the risk of developing cardiovascular disease. We designed to investigate the association of acute MI (AMI) with a polymorphism in the human MMP-1, 2, 3, and 9 genes in Iranian patients with AMI. METHODS: Genomic DNA of 400 enrolled patients with AMI and 200 controls was extracted from their blood samples. The -1607 1G/2G MMP-1, -1306 C/T MMP-2, -1171 5A/6A MMP-3, -1562 C/T MMP-9 polymorphisms were detected. Plasma levels of MMPs were analyzed. RESULTS: There are significant differences in MMP-3 '5A' allele and genotype in the patients with AMI comparing with controls. However, no significant differences were observed in MMP-1, 2, and 9 allele frequencies between the patients and controls. Differences between plasma levels of MMPs were significant in the patients than in controls. There were statistically significant differences between plasma MMP-3 in carriers of 5A allele compared with 6A allele. MMP-9 plasma levels were significantly higher in the carriers of -1306 TT and -1306 CT than CC. However, there were no statistically significant association between genetic variation of MMP-1, 2, and 3 in the patients and their plasma levels. CONCLUSION: These data suggest that MMP genotyping such as genetic polymorphism in MMP-3 might be helpful in determining susceptibility to AMI in Iranian patients. In addition, susceptibility to AMI might be related to MMP-9 gene expression, which affects its plasma levels.