Identification of potential microRNA markers related to Crimean-Congo hemorrhagic fever disease.

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease caused by the arbovirus Crimean-Congo hemorrhagic fever virus (CCHFV). The CCHFV has a single-stranded RNA genome of negative sense. MicroRNAs (miRNAs) are key players in virus-host interactions and viral pathogenesis. We investigated the miRNA gene expression profiles in patients with CCHF using microarray for the first time in the world. Microarray analysis was performed using mirBase Ver 21 (Agilent Technologies, Santa Clara, CA). All statistical analyses were performed across the case-control, fatal-control, and fatal-nonfatal case groups using Genespring (Ver 3.0). Fifteen miRNAs were statistical significant in patients with CCHF compared with the controls (5 were upregulated, 10 were downregulated). Seventy-five and sixty-six miRNAs are in fatal compared with control and nonfatal case, respectively (fold change ([FC] ≥50) were statistically significant. In this study, the target genes of important miRNAs were identified and Gene Ontology analyses were performed across all groups. As a result of this study, we propose that the detection of miRNAs in patients with CCHF will allow the determination of therapeutic targets in diseases. CCHF is an important public health problem that can often be fatal. In this study, we investigated miRNA expression in case-control, fatal-control, and fatal-nonfatal case groups. Significant miRNAs associated with fatality were detected in CCHF. This study will serve as a source of data for the development of an antagomir-based therapy against CCHF using miRNAs in the future.

Regulation of microRNAs in coronary atherosclerotic plaque.

Aim: Identification of microRNAs (miRNAs) associated with atherosclerosis may unravel novel therapeutic targets and biomarkers. We studied miRNAs differentially expressed between coronary atherosclerotic plaques (CAP) and healthy arteries. Materials & methods: Paired CAP and internal mammary arteries (IMA) were collected from 14 coronary artery disease patients. The miRNA profiles between diseased (CAP) and healthy (IMA) tissues were compared using microarrays and quantitative PCR. Results: Thirty-one miRNAs were differentially expressed between CAP and IMA. Among these, miR-486-5p showed a high level of regulation (12-fold), had predicted interactions with atherosclerosis-associated genes and correlated with triglyceride levels and arterial stenosis. Regulation of miR-486-5p was validated by PCR (p = 0.004). Conclusion: The miRNAs are regulated in the atherosclerotic plaque. We highlight miR-486-5p whose role in atherosclerosis requires further investigation.

Effects of MPO-463G/A and -129G/A polymorphisms on coronary artery disease risk and patient survival in a Turkish population.

Myeloperoxidase (MPO) is an oxidative hemoprotein compound expressed in polymorphonuclear leukocytes that contributes to inflammatory responses. Coronary artery disease (CAD), as the most prevalent form of heart disease, is considered to originate from an interaction between genetic and environmental factors. In the present study, the potential associations between MPO-463G/A and -129G/A polymorphisms with CAD were investigated in a Turkish population using a polymerase chain reaction-based restriction fragment length polymorphism (RFLP) assay technique. To the best of our knowledge, the study was the first to examine the association of MPO-463G/A and -129G/A with patient survival rate in a Turkish population. The study population consisted of 201 patients with CAD and 201 healthy controls. The results indicated that there was a significant association of the GA genotype of MPO-463G/A with the case population (P=0.048). Meanwhile, in the patients with CAD, the frequency distributions of the MPO-129A allele (P=0.006) and GA genotype (P=0.001) were significantly increased compared with the G allele and GG genotype, respectively, in CAD patients. Additionally, compared with the GG genotype, the frequency distribution of MPO-129A was significantly increased in the patient group regarding smoking status (P=0.001) and the presence of hypercholesterolemia (P=0.028). However, survival analysis did not detect an effect of either polymorphism on the survival rate of the CAD patients (P>0.05). Therefore, the MPO-129GA genotype may be a significant risk factor for the development of CAD.

Diagnostic usefulness of pregnancy-associated plasma protein-A in suspected pulmonary embolism.

BACKGROUND: The role of biomarkers for prognostication and diagnosis of pulmonary embolism (PE) is increasing. It has been reported that pregnancy-associated plasma protein-A (PAPP-A) can be used as a proatherosclerotic marker. The present study was aimed to evaluate whether PAPP-A levels are helpful in the differential diagnosis of patients presenting with suspected PE. METHODS: 53 consecutive patients evaluated for suspected PE were prospectively enrolled in the study. Serum PAPP-A levels were measured in the blood samples which were taken at admission. Multi-slice computed tomographic angiography was used to verify the diagnosis of PE. RESULTS: PE was detected in 24 out of the 53 patients, while it was excluded in 29 patients by thorax multi-detector computerized tomography scan. No significant difference was detected in mean serum PAPP-A level between groups (5.72 ± 0.31 mg/L vs. 5.67 ± 0.06 mg/L, respectively). CONCLUSIONS: Serum PAPP-A level has no role in the evaluation for PE.

The role of NF-κB1A promoter polymorphisms on coronary artery disease risk.

Coronary artery disease (CAD), which is now regarded as a chronic inflammatory disease, is the leading cause of death worldwide. Nuclear factor (NF)-κB is a transcription factor that plays an important role in the regulation of the immune system. NF-κBIA is the inhibitory version of NF-κB. This study is the first investigation of the association between CAD and NF-κBIA-297 C/T, -826 C/T, -881 A/G polymorphisms in a Turkish population using PCR-RFLP method. The study population comprised 201 cases with CAD and 201 healthy controls. There was no significant difference in NF-κB1A-297 C/T and -881 A/G in allele and genotype frequencies between case and control populations. The genotype frequency of NF-κBIA-826TT in the patients with CAD was significantly higher than that of the controls (p = 0.015, adjusted OR = 7.09, 95% CI = 1.95-25.70). The patients with CAD also had significantly higher carriage rate of NF-κBIA-826T allele than the controls (p = 0.03, OR = 1.43, 95% CI = 1.03-1.99). Linkage analysis indicated a close linkage among these three variants of NF-κBIA (for case, χ(2 ) = 85.35 and p < 0.001; for control, χ(2 ) = 21.58 p < 0.001) and TTG, TTA and TCG haplotypes were associated with CAD (adjusted OR = 2.54, 95% CI = 0.88-7.27; p = 0.001, adjusted OR = 1.61, 95% CI: 0.64-4.02; p = 0.04, adjusted OR = 0.08, 95% CI = 0.01-0.64; p < 0.001, respectively). NF-κBIA-826TT genotype may be a significant risk factor and a valuable marker for the development of CAD.