View clinical trials related to Disease Susceptibility.
Filter by:The objectives of the GECCOS project are to identify genetic variants associated with complications of childhood cancer using genotype-phenotype association studies. Germline genetic samples and data of the "Germline DNA Biobank for Childhood Cancer and Blood Disorders Switzerland" (BISKIDS) which is included in the Geneva Biobank for Hematology and Oncology in Pediatrics (BaHOP) will be used with clinical data of Swiss childhood cancer patients collected at the Institute of Social and Preventive Medicine in Bern.
Tacrolimus (TAC) is characterized by a narrow therapeutic window, as well as high inter- and intra-individual variability in pharmacokinetics. Both under- and overexposure may lead to severe adverse effects. Therapeutic drug monitoring (TDM) is an essential element of post-transplant patient care. Most transplantation centers use C0 to adjust TAC dosage. Some controversies remain about relationship between C0 and clinical outcome. It is generally accepted that only protein-unbound drug molecules can cross cellular membranes, which imply that TDM of free tacrolimus fraction may be of paramount importance and improve clinical management of organ recipients. Whole blood TAC concentrations and dose requirements are strongly associated with CYP3A5 polymorphism. Routine CYP3A5 genotyping on the waiting lists might be useful to guide tacrolimus dosing. This interdisciplinary project tackles the research problem from three angles - biochemistry, genetics and clinical observation. The primary goal of the study is to evaluate clinical usefulness of different TDM protocols in patients after kidney and liver transplantation.
The main objective of this part of the project is to identify the germline genetic factors which discriminate the benign and severe forms of SARS-CoV2 (CoVID-19) infection in the context of the ongoing SARS-CoV2 (HCOVID-19) epidemic. The scientific arguments of the project are described in APPENDIX. We hypothesize that pathogenic variants in genes coding for crucial factors involved in the HOST PATHOGEN interaction could explain the susceptibility of some patients to severe disease, even in the absence of comorbidities. The challenge is to identify those of the genetic factors who may be related respiratory distress and potentially further death. Based on our previous experience in sarcoidosis, a multifactorial disease predisposing to opportunistic infections, we will focus particularly the regulation of apoptosis and autophagy, immune response to viral infection, and endoplasmic reticulum stress response (ER STRESS) which is closely linked to apoptosis. Genetic defects in such pathways may decrease the clearance of viral particles and induces the progressive invasion by SARS-CoV2 and destruction of lung parenchyma. Our strategy will be similar to that described in our previous studies on sarcoidosis, recently published. We will combine a comparative genotype analysis by WHOLE EXOME SEQUENCING (WES) of benign and severe forms of SARS-CoV2 infection through clinical subgroups defined by the infectious diseases experts and a bioinformatics analysis of the functional networks identified by the panel of genes sharing pathogenic variants and discriminating the severe forms of the diseases. WES data will be carefully analyzed and related to all the intracellular physiological process and also the functional pathways involved in host-pathogen interaction: viral targets on the cell surface and downstream signaling, viral genomic RNA replication and translation, production and release of new viral particles. Finally, our main objectives are the definition of a gene panel more specifically related to severe forms of infection and the characterization of defective pathways involved in pejorative forms of SARS-COv2 disease in order to identify putative therapeutic targets.
The aim of the project is to show that gene expression levels change in at least one of the GATA6 and T-box transcription factor 3 (TBX3) genes in indirect inguinal hernia sacs, thus revealing that this pathway causes an error in the sac closure pathway. Indirect inguinal hernia is an important condition for human health as it is common in the community and can lead to life-threatening or permanent loss of function. In addition, since the treatment is performed surgically, the follow-up and treatment process of the patients should be managed carefully in terms of complications and costs. By explaining the mechanisms of the occurrence of this disease, important steps will be taken in terms of both human health and the development of science. Moreover, the data to be collected may open new horizons in the treatment of inguinal hernia. 20 inguinal hernia patients those consecutively applied to Trakya University Medical Faculty Department of Pediatric Surgery and 20 circumcision patients as control group will be included in the study.
Hypnosis is an effective pain management tool for surgery that can reduce opioid use up to 40%. COMT single nucleotide polymorphisms (SNPs) can predict pain sensitivity and opioid use perioperatively, and may also be associated with hypnotizability or response to hypnotic analgesia. Analyzing COMT haplotypes from DNA extracted from saliva or blood using a giant magnetoresistive (GMR) nanotechnology platform may be faster, less expensive, and at least as accurate as pyrosequencing. This study aims to validate a multi-SNP point-of-care (POC) GMR assay for the rapid genotyping of SNPs predictive of COMT activity, and test the feasibility of using COMT activity as a biomarker for hypnotizability and/or response to hypnotic analgesia.
Clinical information and samples (blood, saliva, and tumor) will be collected from patients with multiple cancers and/or a family history of cancer as well as from affected and unaffected relatives; samples will be systematically sequenced and evaluated for candidate driver mutations.
Inherited bleeding disorders (IBD) consist of a heterogeneous group of diseases including coagulation and/or platelets defects and more rarely vascular dysfunctions. A family of four patients suffering from unexplained excessive bleeding has been followed clinically in France for many years. Recently, whole exome sequencing (WES) of DNA allowed the identification of a heterozygous genetic variant which segregated to family members with bleeding diathesis. The aim of the study was to better characterize the phenotype by studying VWF and platelets in affected family members ultimately contributing to the pathogenesis of a bleeding diathesis.
Myocarditis is a complex inflammatory disease, usually occurring secondary to viral infections, autoimmune processes or toxic agents. Clinical presentations are multiple, including chest-pain, heart failure and a broad spectrum of arrhythmias. In turn, outcome is largely unpredictable, ranging from mild self-limiting disease, to chronic stage and progressive evolution towards dilated cardiomyopathy, to rapid adverse outcome in fulminant forms. Subsequently, myocarditis is often underdiagnosed and undertreated, and optimal diagnostic and therapeutic strategies are still to be defined. This study, both retrospective and prospective, originally single-center and subsequently upgraded to multicenter, aims at answering multiple questions about myocarditis, with special attention to its arrhythmic manifestations. 1. Optimal diagnostic workflow is still to be defined. In fact, although endomyocardial biopsy (EMB) is still the diagnostic gold standard, especially for aetiology identification, it is an invasive technique. Furthermore, it may lack sensitivity because of sampling errors. By converse, modern imaging techniques - cardiac magnetic resonance (CMR) in particular - have been proposed as alternative or complementary diagnostic tool in inflammatory heart disease. Other noninvasive diagnostic techniques, like delayed-enhanced CT (DECT) scan or position emission tomography (PET) scan, are under investigation. 2. Biomarkers to identify myocarditis aetiology, predisposition, prognosis and response to treatment are still to be defined. 3. Arrhythmic myocarditis is largely underdiagnosed and uninvestigated. Importantly, myocarditis presenting with arrhythmias requires specific diagnostic, prognostic and therapeutic considerations. At the group leader hospital, which is an international referral center for ventricular arrhythmias management and ablation, a relevant number of patients with unexplained arrhythmias had myocarditis as underlying aetiology. The experience of a dedicated third-level center is going to be shared with other centers, to considerably improve knowledge and management of arrhythmic myocarditis. 4. The role of CMR, as well as alternative noninvasive imaging techniques, in defining myocarditis healing is a relevant issue. In particular, optimal timing for follow-up diagnostic reassessment is still to be defined, in patients with myocarditis at different inflammatory stages, either with or without aetiology-dependent treatment. 5. Uniformly-designed studies are lacking, to compare myocarditis among different patient subgroups, differing by variables like: clinical presentations, myocarditis stage, associated cardiac or extra-cardiac diseases, aetiology-based treatment, associated arrhythmic manifestations, diagnostic workup, and devices or ablation treatment.
Acute stress-induced (takotsubo) cardiomyopathy or broken heart syndrome presents like a heart attack, classically is triggered by intense emotional or physical stress and can have serious health consequences. In the current study the investigators wish to establish whether there is a genetic predisposition making certain people more susceptible to this condition. This could also have implications for their families.
The Childhood Cancer Predisposition Study (CCPS) is a multi-center, longitudinal, observational study that will collect clinical and biological data and specimens from children with a cancer predisposition syndromes (CPS) and their relatives. The central hypothesis is that studying individuals at high risk for childhood cancer creates a unique opportunity for improving the understanding of carcinogenesis, tumor surveillance, early detection, and cancer prevention, which will collectively contribute to improving care and outcomes for pediatric patients with cancer and those with cancer predisposition syndromes (CPS).