A gender dimorphism in up-regulation of BACE1 gene expression in schizophrenia.

Schizophrenia has long been considered as a devastating brain disorder in which both genetic and environmental factors are involved. The BACE1 gene is one of the most important susceptibility genes for this disorder. However, the changes in BACE1 expression in schizophrenic patients compared with healthy subjects have not been evaluated yet. In this case-control study, we examined BACE1 expression in a group of 50 patients with schizophrenia and 50 healthy controls. The level of BACE1 gene expression was measured using Real-Time PCR. Substantial increase in gene expression was detected in the patients compared with normal individuals (P = 0.001). Furthermore, a gender dimorphism was observed in BACE1 gene expression in the patients in a way that the male patients manifested a statistically significant higher levels of BACE1 expression (P = 0.002). BACE1 might be implicated in the pathogenesis of schizophrenia. Besides, BACE1 physiology may be gender -based at some levels. Our findings warrant an investigation of BACE1 gene in a larger number of cases and controls.

Up regulation of MMP9 gene expression in female patients with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an inflammatory, immune-mediated, demyelinating disease of the central nervous system which disturbs cerebral vascular permeability. OBJECTIVE: Matrix metalloproteinase can increase capillary permeability and are involved in neurological diseases. METHODS: The study compared the expression level of MMP9 gene in RRMS samples with normal individuals in Iran. RNA from the buffy coat of 50 RRMS patients and 50 normal controls were extracted. All patients were HLA-DRB1*15 negative and were responders to interferon-beta with a normal vitamin D level. The level of MMP9 gene expression was measured using quantitative RT-PCR. RESULTS: The RRMS patients manifested a higher expression level of MMP9 than their normal counterparts (P= 0.02). Age-wise, there was no correlation between different age groups (> 30, 30-40, 40 <). In terms of sex, only the female patients manifested a statistically significant increase in MMP9 (p value = 0.037). Besides, there was no linear correlation between MMP9 expression level and risk of Expanded Disability Status Scale of Kurtzke (EDSS); nor were there any significant correlation between expression status of MMP9 and duration of the disease. CONCLUSION: Up regulation of MMP9 gene expression would happen in RRMS IFN-B responders, but the level of increase in female patients is significantly more than males.

Association of transforming growth factor-ß1 gene polymorphisms with genetic susceptibility to acute myocardial infarction.

INTRODUCTION: Transforming growth factor beta 1 (TGF-ß1) gene plays an important role in acute myocardial infarction (AMI); however, little is known about the relation of variations within the gene and risk of cardiovascular diseases. In this study, the authors evaluated the influence of TGF-ß1 polymorphisms on the onset and progression of AMI in Iranian patients comparing with healthy individuals. METHODS: Genomic DNA and peripheral blood mononuclear cells of 900 enrolled patients with AMI and 900 control subjects were extracted. The -509 C/T, 868T/C, 913G/C and 11929C/T TGF-ß1 polymorphisms were detected. The messenger RNA (mRNA) expression and serum levels of TGF-ß1 were analyzed by real-time reverse-transcriptase polymerase chain reaction and ELISA, respectively. RESULTS: The frequency of "T" allele in -509 C/T, "C" allele in 868T/C, "C" allele in 913G/C and "T" allele in 11929C/T polymorphisms were significantly higher in the patients than control subjects (P < 0.001). There were significant differences in circulating levels of TGF-ß1 in the patients than in control subjects (P < 0.001). These concentrations are associated with its gene polymorphism. The mRNA expression levels of TGF-ß1 were significantly higher in the patient serums compared with controls (P < 0.001). CONCLUSIONS: Our results confirmed the association between the TGF-ß1 polymorphisms and risk of AMI, which suggest that genetic polymorphisms in TGF-ß1 might be helpful for determining susceptibility to AMI in Iranian patients. There are also significant relationship between serum TGF-ß1 and occurrence of AMI. In addition, susceptibility to AMI might be related to TGF-ß1 gene expression, which affects its serum levels.

Association of Helicobacter pylori infection with acute myocardial infarction.

OBJECTIVES: Helicobacter pylori infection has been linked to cardiovascular diseases (CVD) and several studies have reported its positive association with inflammatory response after acute myocardial infarction (AMI). On account of the importance of the inflammatory process in the development of CVD, we decided to examine the seroprevalence of H. pylori, the prevalence of CVD risk in the more virulent strains bearing the cytotoxin-associated protein (CagA), and the changes in C-reactive protein (CRP) as an inflammatory marker in Iranian patients with AMI. METHODS: A case-control study was designed to determine the seropositivity status of H. pylori and CagA in blood samples obtained from 500 patients with AMI and 500 control individuals without any evidence of clinical CVD. Serum and peripheral blood mononuclear cells were analyzed using the enzyme-linked immunosorbent assay and western blotting methods, respectively. CRP levels were also measured in all individuals. RESULTS: The prevalence of H. pylori infection and CagA status were significantly higher among the patients with AMI than the controls (66 vs. 20% and 75.7 vs. 30%, respectively); the odds ratio was 2.57 (95% confidence interval 1.89-3.49). CRP levels were significantly different in the patients compared with the controls (5.02±1.04 mg/l vs. 2.41±0.9 mg/l, respectively). CONCLUSION: Our results confirmed that the patients with AMI had a significantly higher prevalence of H. pylori infection and CagA seropositivity than the control population. Infection with H. pylori may influence AMI, which in our findings shows an association between H. pylori seropositivity and AMI through an inflammatory process.

Activation of mitogen activated protein kinases in post-infarcted patients.

Activation of mitogen-activated protein kinases (MAPKs) signaling cascade are important pathophysiologic regulators during the development of acute myocardial infarction (AMI). In present study, we designed to monitor the activity of these MAPKs in Iranian patients with AMI comparing with controls. The degree of activation (phosphorylation) of p38 kinase, p44/42 extracellular regulated kinase, and c-Jun N-terminal kinase (JNK1/2) and their corresponding activity levels were analyzed in 258 patients with AMI and 250 normal subjects. The expression of p38α mRNA was determined. These analysis were carried out immediately and 12 h after AMI. Activity of p38 and JNK1/2 MAPKs were significantly increased in patients with AMI than controls immediately after infarction. These activities were reduced during 12 h after AMI. However, there were no statistically differences in activation and activity of p44/42 in the patients and controls. The mRNA expression of p38α was increased in the patients comparing with controls. Results of this study indicate that these MAPKs signaling pathway might be activated by AMI which signal transduction involves kinase phosphorylation and play important roles in their activity. Elevated activity of p38 and JNK1/2 MAPKs suggests that they may potentially play significant roles in AMI.