Long noncoding RNA expression analysis in Crimean Congo hemorrhagic fever patients.

Crimean Congo hemorrhagic fever (CCHF) is an acute viral infection that can cause death. The detection of host transcriptome is important for understanding differences in the pathogenesis of the disease. Long noncoding RNAs (lncRNAs) regulate gene expression in different biological processes. They have also emerged as key molecules for therapeutic targets. We investigated the lncRNA gene expression profiles by utilizing the microarray for the first time in CCHF. LncRNAs were determined by the comparisons between case-control, fatal case-control, and fatal case-nonfatal cases. Quantitative polymerase chain reaction was applied to validate the microarray results of some lncRNAs. In our study, 39 lncRNAs (5 downregulated and 34 upregulated) were found to be significantly regulated in the cases when compared to the controls (p < 0.05; FC ≥ 2). One hundred ten lncRNAs exhibited a statistically significant difference between fatal cases and controls. FER1L4, ECRP, and LOC100133669 are important lncRNAs in both case and fatal case groups compared with controls. These lncRNAs may be considered important therapeutic targets for the CCHF in further studies.

MicroRNA analysis from acute to convalescence in Crimean Congo hemorrhagic fever.

Crimean Congo hemorrhagic fever (CCHF) is one of the most important viral infections and is caused by Crimean Congo hemorrhagic fever orthonairovirus (CCHFV). Severity of CCHF can vary from a mild and nonspecific illness to a severe disease with fatal outcomes. MicroRNAs (miRNAs) have an increasing impact on the different pathways of viral infections. Within the transition process from acute phase to convalescence with 18 CCHF patients, we investigated the impacts on miRNA via microarray for the first time. We also compared miRNA gene expression in 16 severe and 15 mild cases. We identified Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathways associated with significant miRNAs utilizing DIANA TOOLS mirPath v.3. In this study, miR-15b-5p and miR-29a-3p were significantly downregulated in statistical terms; miR-4741, miR-937-5p, miR-6068, miR-7110-5p, miR-6126, and miR-7107-5p were upregulated in acute cases in comparison with convalescent patients (p ≤ .05). In total, 28 miRNAs (8 downregulated, 20 upregulated) were differentially expressed in severe CCHF patients as compared with mild cases (p ≤ .05). Whereas miR-6732-3p, miR-4436b-5p, miR-483-3p, and miR-6807-5p had the highest downregulation, miR-532-5p, miR-142-5p, miR-29c-3p, and let-7f-5p had the highest upregulation in severe patients in comparison with mild cases. Consequently, we determined that CCHF-induced miRNAs are associated with antiviral and proinflammatory pathways in acute and severe cases. In comparison with convalescence, these miRNAs in acute period may be therapeutic targets.

Investigation of NEAT1, IFNG-AS1, and NRIR expression in Crimean-Congo hemorrhagic fever.

Crimean-Congo hemorrhagic fever (CCHF), whose causative agent is CCHF orthonairovirus (CCHFV), demonstrates different symptoms in patients. Long noncoding RNAs (lncRNAs) take part in various pathological processes of viral diseases. They are prominent regulators of antiviral immune responses. To our knowledge, this study is the first study to investigate nuclear paraspeckle assembly transcript 1 (NEAT1), interferon (IFN) gamma antisense RNA 1 (IFNG-AS1), and negative regulator of IFN response (NRIR) expression in CCHF in the literature. We selected these lncRNAs because they are related to IFN signal or IFN-stimulated genes. We investigated NEAT1, IFNG-AS1, and NRIR gene expression in patients with CCHF. Total RNA was extracted from blood samples of 100 volunteers and NEAT1, IFNG-AS1, and NRIR expression were measured using a quantitative real-time polymerase chain reaction. NRIR expression was statistically significant in cases versus controls (p < .001), fatals versus controls (p < .001), and fatals versus nonfatals (p = .01). Furthermore, NRIR was found statistically significant at some clinical parameters including alanine aminotransferase (p = .03), international normalized ratio (p = .03), prothrombin time (p = .02), and active partial thromboplastin time (p = .01) in CCHF cases. NEAT1 and IFNG-AS1 expression were downregulated in the case and fatal groups which were compared with controls. Our results demonstrate that NRIR may be important in CCHF pathogenesis and the target of CCHF treatment.

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.

Effect of TLR10 (2322A/G, 720A/C, and 992T/A) polymorphisms on the pathogenesis of Crimean Congo hemorrhagic fever disease.

Crimean Congo hemorrhagic fever (CCHF) is a tick-borne disease caused by the Crimean Congo hemorrhagic fever virus (CCHFV). Toll-like receptors (TLRs) are type 1 transmembrane proteins of immune cells that play a critical role in innate and adaptive immunity. The present study first time aims to investigate the relation between TLR10 gene polymorphisms (720A/C, 992T/A, and 2322A/G), severity/non-severity, fatality/non-fatality, and CCFH disease by using PCR-RFLP assay in a Turkish population. TLR10 720A/C polymorphism was determined to be statistically significant both genotype and allele frequency (P = 0,011, P = 0.015, respectively). TLR10 992T/A polymorphism was found statistically significant relationships between patient and control (P = 0.026) and individual with AA genotype have approximately three times greater risk than TT genotype (OR = 2.93). There was not a significant difference in 2322A/G genotype distribution (P = 0.152). There were also statistically significant associations between both TLR10 992T/A and 2322A/G polymorphism and patient mortality (P = 0.001 and P = 0.008, respectively). We have not found statistically any linkage among TLR10 haplotype, but individual AAA and GAT haplotype have higher risk than individual AAT haplotype (OR = 3.22, OR = 1.93, respectively). Consequently, this study shows that pathogenesis of CCHF disease is associated with the TLR10 720A/C and 992T/A polymorphisms. There is a statistically significant association in fatal/non-fatal patients with TLR10 720A/C and 992T/A. The TLR10 992AA genotype might increase and TLR10 720CC genotype might decrease susceptibility to pathogenesis of CCHF disease. TLR 10 polymorphisms may be also an important biomarker for CCHF susceptibility and fatality rate.

HULC and 7SL RNA expression levels in patients with Crimean-Congo hemorrhagic fever.

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease caused by the Crimean-Congo hemorrhagic fever virus. Long non-coding RNAs (lncRNAs) are generally classified as transcripts longer than 200 nucleotides (nt). The various lncRNAs expressed in infected cells are responsible for regulating the expression of viral and host genes. This is the first study to investigate hepatocellular carcinoma upregulated long non-coding RNA (HULC) and 7SL RNA expression levels in patients with CCHF. Blood samples were taken from 100 individuals (60 patients and 40 controls), and total RNA isolation was performed. Quantitative polymerase chain reaction (qPCR) was performed using the SYBR Green method to determine HULC and 7SL RNA expression levels in the study population. Compared the patient and control groups, HULC was upregulated statistically significantly (P = 0.04) and 7SL RNA was downregulated (P = 0.93) in patients. Also, there was a statistically significant difference between fatal cases and surviving patients for HULC and 7SL RNA (P < 0.01 and P = 0.03, respectively). In addition, HULC expression was increased statistically significantly in fatal cases compared with surviving patients in terms of clinical parameters such as aspartate aminotransferase (P < 0.01), alanine aminotransferase (P < 0.01), international normalized ratio (P = 0.05), prothrombin time (P = 0.01), active partial thromboplastin time (P < 0.01), and lactate dehydrogenase (P < 0.01). These findings highlighted that HULC and 7SL RNA could be important mediators for studying the pathogenesis of CCHF and significant therapeutic targets of the disease.

MicroRNA-221/222 expression in atherosclerotic coronary artery plaque versus internal mammarian artery and in peripheral blood samples.

BACKGROUND: Atherosclerosis is a disease of the arterial wall with predilection to some sites on others. MicroRNAs (miRNAs) are a class of the non-coding RNAs regulating the target gene expression at post-transcriptional level. Different miRNAs were found at distinct stages of plaque development and expression of miRNAs' might play an important role in the local behaviour of atherosclerotic plaques. OBJECTIVE: We aimed to investigate and compare mirR-221/222 expression levels in tissues and in circulation in patients with and without overt atherosclerosis. METHODS: RNA was isolated from 40 tissues as 20 tissue samples from coronary artery atherosclerotic plaques (CAAP) and internal mammary arteries (IMA), obtained from same individual) and 80 blood (44 patients with atherosclerosis and 36 healthy subjects) samples. MiR-221/222 expression levels were measured using real time PCR. RESULTS: Expression levels of miR-221 was significantly increased in CAAP compared with completely atherosclerosis-free IMA tissues with a 8.94 times fold-change (p = 0.015). The miR-221 expression in tissue samples was significantly different in patients with hypercholesterolemia (p = 0.010), hypertension (p = 0.018) and family history of CAD (p = 0.033) versus not. Expression of miR-222 was not statistically significant between the two tissue samples overall. CONCLUSIONS: MiR-221 may be a potential biomarker for local atherosclerotic behavior.

Is there any relationship between Toll-like receptor 3 c.1377C/T and -7C/A polymorphisms and susceptibility to Crimean Congo hemorrhagic fever?

Crimean-Congo hemorrhagic fever (CCHF) is an infectious disease that is caused by CCHF virus. A family of transmembrane receptors called as Toll-like receptors (TLRs) selectively acts in recognizing a wide range of microbial components and endogenous molecules released by damaged tissue and have been preserved throughout evolution. TLRs initiate some signaling cascades which activate the innate immune system. Mainly four TLRs act in protection against viral infections; TLR3 is one of them. TLR3 identifies dsRNA. By producing inflammatory cytokines and type I interferons, it generates an antiviral immune response. Proper response to TLR ligands may be impaired by single nucleotide polymorphisms (SNPs) within TLR genes in some indviduals, and this can cause varied susceptibility to infections. In the present work, polymerase chain reaction-based restriction fragment length polymorphism is used to analyze the frequencies of TLR3 (c.1377C/T and -7C/A) polymorphisms in 149 CCHF patients and 171 healthy adults as controls, in Cumhuriyet University, Sivas/Turkey. We also investigated the relation between these polymorphisms and severity or mortality of CCHF disease. This is the first study investigating the TLR3 SNPs in patients with CCHF. In the present study, the frequency of the TLR3 (c.1377C/T and -7A/C) genotypes in fatal and non-fatal cases were comparable, however, the homozygous mutant (TT) genotype frequency of TLR3 c.1377C/T in CCHF patients was significantly higher than that of the healthy controls. In conclusion, presence of TLR3 c.1377 TT genotype may have a role in the susceptibility to CCHF. J. Med. Virol. 88:1690-1696, 2016. © 2016 Wiley Periodicals, Inc.

Toll-like receptor 7 Gln11Leu, c.4-151A/G, and +1817G/T polymorphisms in Crimean Congo hemorrhagic fever.

Crimean-Congo hemorrhagic fever (CCHF) is a viral zoonosis. Toll-like receptors (TLRs) initiate signaling cascades leading to the activation of the innate immune system following CCHF infection. In this study, TLR7 (Gln11Leu, c.4-151A/G, and +1817G/T) polymorphisms were investigated in CCHF patients using polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP). The study population comprised 149 CCHF patients and 171 controls. For the TLR7 Gln11Leu polymorphism, there was no significant difference between the case and control groups in allele (P = 0.144) and genotype frequencies (P = 0.219). In the TLR7 IVS1 +1817G/T polymorphism, a statistically significant difference was found in allele frequencies (P = 0.026), but there was no significant difference in the TLR7 c.4-151A/G polymorphism (P = 0.310). There was a statistically significant difference in the distribution of the TLR7 c.4-151GG genotypes frequencies between patients and controls (P = 0.042; OR = 2.23). Furthermore, there were statistically significant associations between the TLR7 c.4-151A/G polymorphism and both severe disease and patient mortality (P < 0.001 and P = 0.047, respectively). The TLR7 IVS1 +1817TT genotype was also significantly associated with the case group but not the control group (P = 0.045). A strong positive linkage among TLR 7 variants was found using haplotype analysis. The incidence of two haplotypes, AGG and AGT, was determined to exhibit significant differences between the case and control groups (P < 0.001 and P < 0.001, respectively). These findings suggest that the TLR7 IVS1 +1817G/T and TLR7 c.4-151A/G polymorphisms may be important in the susceptibility or clinical course of CCHF disease.

Relationship of Toll-Like Receptor 7, 9, and 10 Polymorphisms and the Severity of Coronavirus Disease 2019.

Coronavirus disease 2019 (COVID-19) is a pandemic that is still affecting people and has caused many deaths. Toll-like receptors (TLRs) have an important role in the binding of disease agents to the host cell, disease susceptibility and severity, and host disease resistance. In this study, we investigated the frequencies of TLR7 (C.4-151 A/G), TLR9 (T-1486C and G2848A), and TLR10 (720A/C and 992T/A) single nucleotide polymorphisms in 150 cases with COVID-19 and 171 control samples. We also examined whether TLR7, TLR9, and TLR10 were related to COVID-19 severity. Furthermore, we analyzed the association between COVID-19 and some clinical parameters. Polymerase chain reaction based on restriction fragment length polymorphisms performed for the TLR7, TLR9, and TLR10 single nucleotide polymorphisms. TLR7 C.4-151 A/G G allele and GG genotype; TLR9 T-1486C C allele and TC, CC genotypes; and TLR10 720A/C C allele; TLR10 992T/A A allele and AA genotype frequencies were statistically significant in cases with COVID-19 compared with controls (P < 0.05*). In addition, there was a statistically significant difference in the distribution of TLR7, TLR9, and TLR10 allele and genotype frequencies between the severity groups (P < 0.05*). Our findings suggest that TLR7, TLR9, and TLR10 polymorphisms may be crucial for the clinical course and susceptibility to infection.

Role of lncRNAs in Remodeling of the Coronary Artery Plaques in Patients with Atherosclerosis.

INTRODUCTION: Cardiovascular diseases (CVDs) are the leading cause of death worldwide according to World Health Organization (WHO) data. Atherosclerosis is considered as a chronic inflammatory disease that develops in response to damage to the vascular intima-media layer in most cases. In recent years, epigenetic events have emerged as important players in the development and progression of CVDs. Since noncoding RNA (ncRNAs) are important regulators in the organization of the pathophysiological processes of the cardiovascular system, they have the potential to be used as therapeutic targets, diagnostic and prognostic biomarkers. In this study long noncoding RNA (lncRNA) and mRNA gene expression were compared between coronary atherosclerotic plaques (CAP) and the internal mammary artery (IMA)  which has the same genetic makeup and is exposed to the same environmental stress conditions with CAP in the same individual. METHODS: lncRNA and mRNA gene expressions were determined using the microarray in the samples. Microarray results were validated by RT-qPCR. Differentially expressed genes (DEGs; lncRNAs and mRNAs) were determined by GeneSpring (Ver 3.0) [p values < 0.05 and fold change (FC) > 2]. DAVID bioinformatics program was used for Gene Ontology (GO) annotation and enrichment analyses of statistically significant genes between CAP and IMA tissue. RESULTS AND CONCLUSIONS: In our study, 345 DEGs were found to be statistically significant (p < 0.05; FC > 2) between CAP and IMA. Of these, 65 were lncRNA and 280 were mRNA. Thirty-three lncRNAs were upregulated, while 32 lncRNAs were downregulated. Some of the important mRNAs are SPP1, CYP4B1, CHRDL1, MYOC, and ALKAL2, while some of the lncRNAs are LOC105377123, LINC01857, DIO3OS, LOC101928134, and KCNA3 between CAP and IMA tissue. We also identified genes that correlated with statistically significant lncRNAs. The results of this study are expected to be an important source of data in the development of new genetically based drugs to prevent atherosclerotic plaque. In addition, the data obtained may contribute to the explanation of the epigenetic mechanisms that play a role in the pathological basis of the process that protects the IMA from atherosclerosis.

Relationship between NF-κB1 and NF-κBIA genetic polymorphisms and Crimean-Congo hemorrhagic fever.

BACKGROUND: Crimean-Congo hemorrhagic fever (CCHF) is an acute viral hemorrhagic fever caused by the Crimean-Congo hemorrhagic fever virus (CCHFV). Nuclear factor (NF)-κB regulates the expression of hundreds of genes, including inflammatory and immunoregulatory, cell cycle regulating, and anti-apoptotic genes. NF-κBIA (IκBα) encodes an inhibitory version of the NF-κB proteins. METHODS: This study is the first to investigate the association between NF-κB1 - 94W/D and NF-κBIA 3→UTR A→G polymorphisms and CCHF using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: There was a significant difference in NF-κB1 - 94W/D genotype distribution between CCHF patients and control populations (p = 0.001). Comparison of the WW genotype with both WD and DD genotypes revealed that the difference between CCHF patients and controls was statistically significant (p = 0.043 for WD genotype, p = 0.018 for DD genotype). However, a significant deviation was found between patients with fatal CCHF and control populations (p = 0.025). The results show that patients with fatal CCHF with the DD genotype have a 4.06-times higher risk for CCHF compared to patients in the control group (odds ratio (OR) 4.06, 95% confidence interval (CI) 1.11-14.87). A significant difference in NF-κBIA 3→UTR A→G polymorphisms was observed between CCHF patients and controls in both AA vs AG and AA vs GG (OR 2.04, p = 0.019; OR 2.01, p = 0.049, respectively). CONCLUSIONS: Our findings suggest that NF-κB1 - 94W/D and NF-κBIA 3→UTR A→G polymorphisms may be valuable predictors of the clinical course in CCHF disease.

Research on Hotair and 7SL-RNA Gene Expression Levels in Psoriasis Vulgaris.

Backgrounds: Mutation of protein-coding genes and non-coding genes is a factor in psoriasis etiology. Non-coding RNA (ncRNA), which does not have protein-coding capacity, is available in the human genome. HOTAIR (HOX Antisense Intergenic RNA) and 7SL-RNA are known as ncRNA. They may play a role in psoriasis pathogenesis. Aims: In our study, we aimed to investigate the level of HOTAIR and 7SL-RNA gene expression in the lesional and perilesional healthy skin of psoriasis patients. Methods: Total RNA isolation from the skin samples was achieved by modifying the RNeasy Mini Kit (Qiagen, Cat No: 74104) protocol. Real Time Polymerase Chain Reaction (qPCR) phase was performed in accordance with the protocol of the relevant brand (WizPure qPCR). Results: 7SL-RNA gene expression decreased in the skin with psoriatic lesions (FC: 0.01; p: 0.028), and this decrease was statistically significant. HOTAIR gene expression decreased (FC: 0.92; p: 0.218), but this decrease was not statistically significant. Conclusions: lncRNAs may play a role in the pathogenesis of psoriasis disease.

Genetic polymorphisms of sulfotransferases (SULT1A1 and SULT1A2) in a Turkish population.

Sulfotransferases (SULTs) play a significant role in the biotransformation of a variety of xenobiotics and endogenous compounds. SULTs are genetically polymorphic enzymes; to date, 12 human cytosolic SULT isoforms have been identified. This study investigated SULT1A1 and SULT1A2 gene polymorphism using a PCR-RFLP method (n = 303). The frequency of the SULT1A1*1 allele was 76.2% and SULT1A1*2 was 23.8%. The SULT1A1*3 allele could not be identified. The SULT1A2 frequencies were 69.2% (SULT1A2*1), 18.3% (SULT1A2*2), and 12.5% (SULT1A2*3). The SULT1A1 and SULT1A2 loci were in Hardy-Weinberg equilibrium (SULT1A1 χ² = 0.58, P = 0.44; SULT1A2 χ² = 7.28, P = 0.06). Linkage analysis indicated a close linkage between these two genes (χ² = 5.31, P < 0.01); therefore, the statistical hypothesis that SULT1A1 and SULT1A2 alleles are independently distributed was rejected. Additionally, a strongly positive linkage was detected between SULT1A1*2 and SULT1A2*2 alleles in this population (D' = 0.79, χ² = 33.33).

Genetic structure of brown trout (Salmo trutta) populations from Turkey based on microsatellite data.

This present study investigated micro- and macro-geographic microsatellite DNA variations using five polymorphic microsatellite loci from 27 brown trout populations in Turkey. Average number of alleles and average observed heterozygosity were 7.4 and 0.254, respectively. Even populations from the same sea basin and river system (the so called micro-geographic regions) had unique alleles. Genetic variation among the populations from macro-geographic regions (different sea basins and river systems) was 45.78%. The mtDNA lineages of brown trout that have previously been identified by mtDNA analyses were supported by the analysis of the microsatellite DNA data in general. The Çatak population, which belongs to the Tigris lineage, was clustered together with the Euphrates populations within the Adriatic mtDNA lineage, based on microsatellite data. Both mitochondrial and microsatellite DNA analyses have made it possible to determine a secondary contact between Adriatic and Tigris lineages.

An investigation of the relationship between SULT1A1 Arg(213)His polymorphism and lung cancer susceptibility in a Turkish population.

Human sulfotransferase 1A1 (SULT1A1), the most expressed isoform of the phenol SULT1 subfamily, is an important member of sulfotransferase superfamily. A transition, G to A at position 638, in SULT1A1 gene, results in Arg(213)His change. This single nucleotide polymorphism reduces the activity and thermostability of SULT1A1 enzyme. Thus, in the present study the relationship between SULT1A1 Arg(213)His polymorphism and lung cancer was investigated. One hundred and six case and 271 control samples were studied using PCR-RFLP. There was no significant difference in genotype and allele distribution between lung cancer and control populations (p = 0.07; p = 0.06, respectively). Compared with the SULT1A1*1/SULT1A1*1 genotype the variant SULT1A1 genotype (SULT1A1*1/SULT1A1*2 or SULT1A1*2/SULT1A1*2) was associated with a significantly increased lung cancer risk in cases (p = 0.027). In male populations, there was no significant difference between case and controls (p = 0.313). In female populations, however, this difference was found to be significant (p = 0.04). In smoker and non-smoker populations, no significant relationship was evident between lung cancer and control population (p = 0.170, p = 0.065, respectively). Statistical analyses of histological types of lung cancer in comparison with the control individuals indicated a significant difference between SULT1A1 Arg(213)His polymorphism and SCC (p = 0.027) and other types of cancer (p = 0.037), except SMCC (p = 0.854).

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.

Catalyzing Transcriptomics Research in Cardiovascular Disease: The CardioRNA COST Action CA17129.

Cardiovascular disease (CVD) remains the leading cause of death worldwide and, despite continuous advances, better diagnostic and prognostic tools, as well as therapy, are needed. The human transcriptome, which is the set of all RNA produced in a cell, is much more complex than previously thought and the lack of dialogue between researchers and industrials and consensus on guidelines to generate data make it harder to compare and reproduce results. This European Cooperation in Science and Technology (COST) Action aims to accelerate the understanding of transcriptomics in CVD and further the translation of experimental data into usable applications to improve personalized medicine in this field by creating an interdisciplinary network. It aims to provide opportunities for collaboration between stakeholders from complementary backgrounds, allowing the functions of different RNAs and their interactions to be more rapidly deciphered in the cardiovascular context for translation into the clinic, thus fostering personalized medicine and meeting a current public health challenge. Thus, this Action will advance studies on cardiovascular transcriptomics, generate innovative projects, and consolidate the leadership of European research groups in the field.COST (European Cooperation in Science and Technology) is a funding organization for research and innovation networks (www.cost.eu).

Decreased FENDRR and LincRNA-p21 expression in atherosclerotic plaque.

OBJECTIVE: Cardiovascular diseases are the most important cause of mortality worldwide, particularly atherosclerosis. Recently, lncRNAs affecting atherosclerotic progression have been reported in vascular smooth muscle cells, endothelial cells, and monocytes, suggesting that lncRNAs play an important role in atherosclerosis. METHODS: In recent clinical studies, nowadays, it was determined that internal mammary bypass grafts are closest to ideal grafts in coronary artery bypass surgery. In this study, we used tissue samples taken from atherosclerotic coronary arteries and the internal mammary artery (IMA) during coronary artery bypass surgery. Using RT-PCR, we investigated the role of two lncRNAs, FENDRR and LincRNA-p21, by comparing their expression levels in coronary artery plaques and normal mammary arteries of 20 atherosclerotic patients. RESULTS: We found that the FENDRR and LincRNA-p21 expressions decreased by approximately 2 and 7 fold in coronary artery plaques, respectively, compared with those in IMA, which is known to have no plaque development. CONCLUSION: This study was the first to use mammary artery tissues of the same patients as a control and to study FENDRR expression. Our data may provide helpful insights regarding the association of lncRNAs and atherosclerosis.

FOXP3 rs3761548 polymorphism is associated with knee osteoarthritis in a Turkish population.

AIM: Functional polymorphisms located in FOXP3 intron 1 was recently found to be associated with rheumatoid arthritis (RA). Although RA is an autoimmune disease, there is supporting evidence that activated maladaptive responses including pro-inflammatory pathways play roles in osteoarthritis (OA), similar to RA. The aim of this study was to explore the relationship between rs2232365 (-924A/G) and rs3761548 (-3279A/C) polymorphisms as well as possible changes in the 600 bp promoter region of FOXP3 and knee OA. METHODS: Patients with primary knee OA (n = 300) and healthy individuals (n = 300) were examined for rs3761548 and rs2232365 FOXP3 gene polymorphisms by the polymerase chain reaction-restriction fragment-length polymorphism method. The 600 bp promoter region (between -500 and +100) of the gene was also sequenced with direct sequencing in 50 knee OA patients and 50 healthy individuals. RESULTS: There were no sequence variants in the promoter region tested both in OA patients and healthy controls. The SNP rs2232365 showed no association with OA susceptibility and severity and the results of other genetic models were also nonsignificant. On the other hand, rs3761548 AC (P = 0.003), AA + CC (P = 0.0014) as well as AC + AA (P = 0.40) genotypes showed association with Grade 4 knee OA patients. CONCLUSION: Our findings indicated that the association between FOXP3 rs2232365 polymorphism and knee OA tended to yield negative results but the FOXP3 rs3761548 C allele was associated with elevated risk of OA in Grade 4 knee OA patients in a Turkish population.