STOX1 promotor region -922 T > C polymorphism is associated with Early-Onset preeclampsia.

Preeclampsia (PE), affecting 5-8% of pregnancies, is a common pregnancy disease that has harmful effects on mother and foetus. It has been found that the STOX1 (Storkhead Box 1), which is a transcription factor, carries variants associated with PE. Previous studies showed that, there was a strong relationship between PE and STOX1 variants. Therefore, we hypothesised that variants in the promoter region of the gene may be related to the onset of PE. The aim of this study is to investigate the contribution of STOX1 gene promoter region variants to PE. The blood samples taken from 118 PE patients and 96 healthy pregnant women were analysed by Sanger sequencing method. Sequence analysis results showed that, there is a-922 T > C polymorphism (rs884181) in the promoter region of the STOX1 gene. This polymorphism was found to be statistically significant in individuals with early onset PE (p = 0.02) and in PE (p = 0.014) compared to the control group.IMPACT STATEMENTWhat is already known on this subject? As a result of whole-exon studies on the STOX1 gene, polymorphisms were found to disrupt the structure/expression/function of the gene and strengthen its relationship with PE and HELLP syndrome. A previous study by our team found an association between Y153H, the most common polymorphism of STOX1, and early onset PE.What do the results of this study add? In our study, it was aimed to investigate the effect of genetic modifications in STOX1 gene promoter region on PE through the maternal genotype. Because any change in the promoter region affects the expression level of the gene. Also, for the first time, sequence analysis of the promoter region of STOX1 is investigated in PE. The variations in STOX1 appear to be important in PE especially in Early Onset PE.What are the implications of these findings for clinical practice and/or further research? Although PE is a disease that occurs with pregnancy and shows its effects most during this period, women and children with a history of PE are more prone to various disorders, especially cardiovascular diseases in the following years. Therefore, understanding the pathogenesis of the disease is important for both prevention and treatment process. Variations on STOX1 appear to be important in terms of disease risk.

The role of two common FOXP3 gene promoter polymorphisms in preeclampsia in a Turkish population: a case-control study.

Preeclampsia (PE), which occurs in approximately 5% of pregnancies worldwide and constitutes clinically serious complications in 2-3%, is one of the leading causes of maternal and prenatal morbidity and mortality. Recent studies report that regulatory T (Treg) cells, which act as immunosuppressant, are associated with PE. It is clearly defined that FOXP3/Scurfin (Forkhead Box P3) is involved in the development and function of Tregs. However, there are different conclusions regarding the relationship between PE and FOXP3 gene polymorphisms for different populations. For this reason, in this study we investigate the association between FOXP3 gene promoter region polymorphisms and PE in a Turkish population 500 PE patients and 500 healthy pregnant women. Blood samples taken from pregnant women were studied by PCR-RFLP method. As a result, rs2232365 polymorphism was significantly associated with disease (p < .0001) while no significant association was found between rs3761548 polymorphism and the disease (p = .17). Based on these results, it is though that FOXP3 rs2232365 polymorphism may be predisposed to PE development in terms of Turkish population. However, further and functional studies are needed in terms of other polymorphisms and mutations.IMPACT STATEMENTWhat is already known on this subject? A number of recent publications suggest that Tregs may play a role in the pathogenesis of PE. It is known that a stable and high FOXP3 expression is required to maintain the suppressive T cell function of Tregs. Down regulation of FOXP3 in PE has been reported in many previous studies, but the mechanism is still uncertain.What do the results of this study add? Our study has examined two FOXP3 promoter region polymorphisms in terms of Turkish population for the first time. Rs2232365 polymorphism associated with the disease in heterozygous genotype.What are the implications of these findings for clinical practice and/or further research? It has been shown that FOXP3 gene promoter region polymorphisms may be associated with PE for Turkish population. Our results can be a guide for more detailed statistical evaluations and functional studies.

Preeclampsia and STOX1 (storkhead-box protein 1): Molecular evaluation of STOX1 in preeclampsia.

Preeclampsia (PE) is clinically defined as a part of pregnancy characterized by hypertension and multiple organ failure. PE is broadly categorized into two types: "placental" and "maternal". Placental PE is associated with fetal growth restriction and adverse maternal and neonatal outcomes. STOX1 (Storkhead box 1), a transcription factor, discovered through a complete transcript analysis of the PE susceptibility locus of 70,000 bp on chromosome 10q22.1. So far, studies investigating the relationship between STOX1 and PE have focused on STOX1 overexpression, STOX1 isoform imbalance, and STOX1 variations that could have clinical consequence. Initially, the Y153H variation of STOX was associated with the placental form of PE. Additionally, studies focusing on the maternal and fetal interface have shown that NODAL and STOX1 variations play a role together in the unsuccessful remodeling of the spiral arteries. Research specifically addressing the overexpression of STOX1 has shown that its disruption of cellular hemoastasis, leading to impaired hypoxia response, disruption of the cellular antioxidant system, and nitroso/redox imbalance. Furthermore, functional studies have been conducted showing that the imbalance between STOX1 isoforms contributes to the pathogenesis of placental PE. Research indicates that STOX1B competes with STOX1A and that the overexpression of STOX1B reverses cellular changes that STOX1A induces to the pathogenesis of PE. In this review, we aimed at elucidating the relationship between STOX1 and PE as well as function of STOX1. In conclusion, based on a comprehensive literature review, numerous studies support the role of STOX1 in the pathogenesis of PE.

Computationally predicted SARS-COV-2 encoded microRNAs target NFKB, JAK/STAT and TGFB signaling pathways.

Recently an outbreak that emerged in Wuhan, China in December 2019, spread to the whole world in a short time and killed >1,410,000 people. It was determined that a new type of beta coronavirus called severe acute respiratory disease coronavirus type 2 (SARS-CoV-2) was causative agent of this outbreak and the disease caused by the virus was named as coronavirus disease 19 (COVID19). Despite the information obtained from the viral genome structure, many aspects of the virus-host interactions during infection is still unknown. In this study we aimed to identify SARS-CoV-2 encoded microRNAs and their cellular targets. We applied a computational method to predict miRNAs encoded by SARS-CoV-2 along with their putative targets in humans. Targets of predicted miRNAs were clustered into groups based on their biological processes, molecular function, and cellular compartments using GO and PANTHER. By using KEGG pathway enrichment analysis top pathways were identified. Finally, we have constructed an integrative pathway network analysis with target genes. We identified 40 SARS-CoV-2 miRNAs and their regulated targets. Our analysis showed that targeted genes including NFKB1, NFKBIE, JAK1-2, STAT3-4, STAT5B, STAT6, SOCS1-6, IL2, IL8, IL10, IL17, TGFBR1-2, SMAD2-4, HDAC1-6 and JARID1A-C, JARID2 play important roles in NFKB, JAK/STAT and TGFB signaling pathways as well as cells' epigenetic regulation pathways. Our results may help to understand virus-host interaction and the role of viral miRNAs during SARS-CoV-2 infection. As there is no current drug and effective treatment available for COVID19, it may also help to develop new treatment strategies.

STOX1 gene Y153H polymorphism is associated with early-onset preeclampsia in Turkish population.

Preeclampsia (PE) is a disease of pregnancy that causes of maternal and prenatal morbidity worldwide. Studies indicate that variations in STOX1 gene may be a direct risk factor to PE but controversial results regarding the relationship of Y153H variation in the second exon of STOX1 gene with PE have been ongoing since 2005. The aim of this study was to identify if there is any correlation between Y153H polymorphisms and PE in Turkish preeclampsia patients. We performed polymerase chain reaction- restriction fragment lengthpolymorphism(PCR-RFLP) analysis in 500 pregnant women, of whom 373 pregnant women with early onset PE (EOPE) and 500 normal pregnant women. The relationship between STOX1 Y153H polymorphism and EOPE/LOPE was evaluated by statistical analysis. We found that STOX1 Y153H polymorphism is a risk factor for EOPE (p = 0.03). The odds ratio was 1,45 (CI 95% = 1,03-2,05). No relationship between STOX1 Y153H polymorphisms and LOPE (p = 0.13) was found. STOX1 gene Y153H polymorphism is associated with the risk ofearly onset of pre-eclampsiain a Turkish population. The results provide further evidence of the role of STOX1 in the pathophysiology of this disease.

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.

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.

MEFV mutations and their relation to major clinical symptoms of Familial Mediterranean Fever.

Familial Mediterranean fever is a common hereditary disease in Turkey. To date, different mutational spectrum of MEFV gene was observed in studies carried out in different regions of Turkey but in most of these studies association of clinical symptoms of FMF to mutant genotypes have not been investigated in details. Here we report the MEFV gene variations in exons 2, 3, 5 and 10 and their relations to major clinical symptoms of FMF in 514 unrelated (245 males and 269 females) Turkish patients. MEFV mutations were found in 45% (n=230) of patients and 55% (n=284) of patients did not have any mutations. One hundred and thirty-seven (60%) patients were heterozygous, 57 (24.7%) patients were compound heterozygous, 33 (14%) patients were homozygous and 3 (1.3%) patients were having a complex genotype. Allele frequencies of MEFV mutations were M694V (48%), E148Q (18%), M680I (15%), V726A (12.5%), P369S (3.3%), R761H (0.9), K695R (0.9), E148V (0.9) and A744S (0.5%). Abdominal pain (76%) and fever (58%) were two most seen complications among patients followed by arthritis (28%) and chest pain (19%). Almost all major clinical symptoms of FMF were higher in patients with one or more M694V or M680I mutant allele. In contrast, patients having E148Q or V726A mutant allele showed fewer clinical FMF symptoms. Patients with P369S have higher abdominal pain, chest pain and fever than expected. Arthritis was high in K695R heterozygous genotype. One hundred and eighteen patients were carrying more than one polymorphic allele. The most common polymorphism was R202Q (13%). In addition, a novel heterozygous polymorphism at 564th nucleotide (C>T) of exon2 were found in 2 patients.