View clinical trials related to Disease Susceptibility.
Filter by:The pathogenesis of CHD remains poorly known despite much research over the last few decades. Numerous non-genetic variables have been demonstrated to have a significant impact on the risk of CHD. However, the fact that many individuals with severe CHD do not have any of these non-genetic risk factors supports the notion that genetic factors play a role in the occurrence and progression of CHD. In this study, we investigated the association of polymorphisms affecting Vascular endothelial factors A (VEGFA) and its receptor VEGFR2 (rs3025039, rs699947, rs2305948, rs1870377), CXCR4 (rs2228014), CCR2 (rs1799864), C3 (rs2230199), CCL2 (rs1024611 and rs2857656) and CCL5 (rs2107538 and rs22280789) with CHD susceptibility and the severity of coronary lesion. On another side, clopidogrel is largely prescribed in association with aspirin in order to prevent atherothrombotic complications in patients with acute coronary syndrome. Its effectiveness is undeniably proven by several studies and clinical trials over the years, however, some patients have presented ischemic events such as thrombosis on stent or myocardial infarction despite a well-conducted treatment. This clopidogrel non-responsiveness is probably multifactorial; several genetic and non genetic factors may contribute to impaired platelet inhibition by clopidogrel. In this regard, it is meaningful to determine genetic polymorphisms contributing to the variability of clopidogrel response in patients with Coronary Artery Therefore, the goal of this study is to determine the impact of the polymorphisms, affecting CYP2C19, PON, ABCB1, ITGB3 and P2RY12 genes, on the response to clopidogrel in patients with CAD.Disease (CAD). In fact, the recognition of these factors might predict the exposure to the risk of thrombosis and cardiovascular death in these patients.
This proposal relates to the testing of several specific hypotheses in a subset of 500 participants in the Canadian Healthy Infant Longitudinal Development (CHILD) Study. These 500 now have complete data from the time of recruitment (in pregnancy) to age 1 year. The primary purpose of this proposal is to identify risk factors for early allergic outcomes and biomarkers that may predict future disease. These 500 infants will provide critical preliminary data, not only related to early outcomes, but also to inform analytical plans for the full CHILD cohort.
This study is evaluating Whole Body MRI as a possible screening tool to diagnose cancer for people with LFS and other inherited cancer predisposition syndromes.
Upon penicillins' introduction, inactivation of beta- lactam antibiotics by enzymes produced by bacteria was demonstrated. Until recently, carbapenems were a relatively spared subclass by these enzymes which makes the molecules of last resort in serious infection. Recently the prevalence of enzymes hydrolysing carbapenem, the carbapenemases, was increasing in some countries. But these carbapenemases are not the only mechanism involved in a decreased susceptibility to carbapenems which is sometimes linked to the conjunction of several resistance mechanisms. Data available on the epidemic situation of this new resistance are essential for improving their detection, the management of infections in patients and prevent the occurrence of epidemic. In this context, the investigators propose a study in the North-East inter-region to estimate the prevalence of Enterobacteriaceae with decrease susceptibility to carbapenems and look for risk factors for infection with this type of bacteria. The study is conducted in five teaching hospitals (Besançon, Dijon, Nancy, Reims and Strasbourg) and two general hospitals (Colmar and Troyes) in North-Eastern France. For one year, all the Enterobacteriaceae isolates with a decreased susceptibility to carbapenems (CDSE) according to the 2012 Antibiogram Comity of the French Microbiology Society (CA-SFM) (MIC of ertapenem > 0.5 μg/mL) are collected and sent to the bacteriology laboratory of the Reims University Hospital. Among these strains 105 are randomly selected. The clinical study is conducted as follow: for each patient with CDSE isolate included in a center, 2 control patients are selected. They are the patients having the 2 Enterobacteriaceae isolates, with no reduced susceptibility to carbapenems and following the CDSE isolate in the same center. Microbiological study : identification of isolates is performed using MALDI-TOF (Bruker Daltonics, Bremen, Germany). Antibiotic susceptibilities is determined by the disc diffusion method according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines (www.EUCAST.org) and extended-spectrum beta-lactamase (ESBLs) are detected by the double-disc synergy test and carbapenem minimal inhibitory concentrations (MICs to Imipenem, Ertapenem, Doripenem and Meropenem) determined using E-test® strips. Metallo-β-lactamase production was screened with the MβL Etest (bioMérieux, Marcy l'Etoile, France). Beta-lactamases detected using polymerase chain reaction (PCR). Carbapenemase-encoding genes (blaKPC, blaVIM, blaIMP, blaNDM, blaOXA-23-like, blaOXA-24-like, blaOXA-58-like and blaOXA-48-like) were screened using multiplex PCRs and blaIMI and blaGES with simplex PCRs. All the blaOXA-48-like detected were subsequently sequenced. Genes blaTEM, blaSHV, blaCTX-M and blaOXA were detected by PCR using specific primers. Plasmid-mediated AmpC-type genes blaACC, blaFOX, blaMOX, blaDHA, blaCMY and blaMIR were screened using multiplex PCRs. All the beta-lactamases are sequenced. Mutations in the quinolone resistance determining region (QRDR) are identified by PCR and sequencing in the gyrA, gyrB, parC and parE genes. Qnr and qepA genes are detected by real-time PCR, aac(6')-Ib-cr by pyrosequencing and oqxAB by conventional PCR. Genotyping is performed with pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Statistical analysis : qualitative variables are analysed with the Chi2 test and the two-tailed Fisher exact test. Quantitative variables are compared using the Mann-Whitney test. Then, a multivariate analysis is conducted: logistic regression with stepwise factors as explanatory variables with p <0.20 in the univariate analysis as input threshold and output set at 0.20.The results are considered statistically significant when P < 0.05. Expected results : this study will give the proportion of the different species involved, of the carbapenemase in comparison to the other mechanisms, the level of resistance in MIC. Risk factors such as previous antibiotic treatment, underlying disease severity or clonal strain transmission will be evidenced, allowing to identify prevention control measure to implement.
Approximately 10% of the world's population have a particular genetic makeup (known as the TT genotype) that may increase their risk of having higher blood pressure. Previous work conducted by the investigators research group at the University of Ulster, in collaboration with clinical colleagues from across Northern Ireland, in premature CVD patients and hypertensive adults generally has demonstrated that a dietary level of riboflavin (1.6mg/d) decreases blood pressure, specifically in those with the TT genotype. To date, the blood pressure lowering effects of higher doses of riboflavin in individuals with the TT genotype is not known. The aim of this study is to investigate whether supplementation with riboflavin at a low dose supplemental level (10mg/d) can decrease blood pressure more effectively than the dietary level (1.6mg/d) by optimising riboflavin status and normalising MTHFR activity. This aim will be achieved by conducting a double-blind placebo-controlled intervention study over a 16 week period. Participants will be recruited from cohorts screened for the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism. Those identified with the TT genotype (homozygous for the polymorphism) that wish to participate in this research will be asked to attend a baseline and week-16 appointment and will be asked to take a daily riboflavin (1.6 or 10mg/d) or placebo capsule for the duration of the study. At each appointment a blood sample will be taken and blood pressure, height, weight and waist circumference will be measured. If the results of this study show that intervention with a higher dose of riboflavin can lower blood pressure more effectively in individuals with the TT genotype this will have important implications for those responsible for the management of blood pressure. The findings will be of particular relevance in populations with a higher prevalence of the polymorphism.
To elucidate the disease pathway of perinatal depression by identifying genetic variants which could play a role in predisposing to the condition and/or lead to better understanding of the pathogenesis of the condition. This is achieved by investigating for associations between oestrogen receptor genetic variants and perinatal depression.
Invasive bacterial infection is a dangerous but relatively uncommon disease where bacteria spread deep into the body causing diseases like blood poisoning ('bacteraemia'), pneumonia, meningitis and others. The various bacteria of the streptococcus family are an important cause, often leading patients to require intensive care despite which, for some strains, one in five patients die. One notable form is called necrotising fasciitis, a condition where bacteria rapidly spreads through and destroys the layers of tissue just under the skin. As individuals vary greatly in their risk of developing such serious infections, investigating how the genome, the inherited blueprint of our bodies, of these patients differs from that of healthy volunteers can help to explain why the disease develops in some and not others. For some streptococcal bacteria such as Streptococcus pneumoniae this approach is already proving successful; for others such as the "Group A" strain (Streptococcus pyogenes) it has yet to be explored but carries excellent potential. The investigators have secured the support of the Lee Spark Necrotising Fasciitis Foundation to recruit from their membership survivors of streptococcal infections and some of their family members. The investigators will also ask infection specialists from NHS hospitals to invite patients they have looked after. The investigators also have a small existing collection. Taking part would involve registering information on a website, discussing the study on the telephone and then providing us with a sample of saliva from which the investigators can isolate DNA. The investigators would prepare the sample for analysis of the genome and compare the patients with both their family and an existing reference collection from healthy volunteers using technology that reads the DNA code. Our study will be a first key step in renewing efforts to understand the determinants of invasive streptococcal infection, which is important for developing better treatments and vaccines.
The goal of this study is to understand factors which may influence risk for colorectal and other cancers in families. These factors include genetic variability, in combination with diet and lifestyle. In order to achieve these goals, we need to contact as many eligible participants as possible.
Lung cancer is the leading cause of cancer deaths in Taiwan. The carcinogen in the environment is a key role in the development of lung cancer, and one of its main resource is tobacco. Activated carcinogens in the organism lead to mutations of crucial oncogenes resulting in tumor development. Genes such as Cytochrome P-450 family, GST (glutathione S-transferase) family, UGT (UDP-Glucuronosyltransferase) family, ERCC-1(excision repair cross-complementing rodent repair deficiency),ERCC-4 and ERCC-5,are encoding antioxidant enzymes or involving in the DNA repair process and the production of some transcription factors. In recent years, many studies have shown the correlation between these genes and the susceptibility of lung cancer. Each gene has a different role in the tumor development pathway. CYP, UGT, GST, NAT2 (N-acetyltransferase 2) and NQO1(NAD(P)H:quinono oxidoreductase 1) involve in the production of antioxidant enzymes. The antioxidant enzymes can detoxificate hydrogen peroxide or defense against oxidative stress. However, the genetic polymorphisms may influence the function of detoxification, which cause the increase in the susceptibility of lung cancer. P53 and MDM2 genes play important roles in the production of tumor-suppression proteins and the regulation of transcription factors, which may regulate the growth and the apoptosis of cell cycle and influence the susceptibility of lug cancer. The polymorphisms in ERCC genes may cause the damage in the DNA repair process which might also cause increase in lung cancer susceptibility. The overexpression of epidermal growth factor receptor is highly correlated with increasing risk of the non-small cell lung cancers. The overexpression may induce the proliferation of cancer cells and the inhibition of the apatosis. Therefore, in recent years, EGFR has been widely studied as the new target of the drugs and the susceptibility of the lung cancer. In addition,the genetic polymorphisms in drug metabolism channel proteins, like OCT2 (organic cation transporter), ATP7A, ATP7B and ABC (ATP-binding cassette) transporter may have influence on the metabolism, the efficacy and the toxicity of the drugs.
During the past two decades, the frequency of invasive fungal infections has increased dramatically in hospitalised patients throughout the world, and Candida has now emerged as one of the leading causes of bloodstream infections (BSIs). Risk-factors for invasive candidiasis include improvements in intensive care strategies (i.e., central venous catheters, mechanical ventilation, hyper-alimentation), prolonged stays in intensive care units (ICUs), the development of more aggressive surgical techniques, and the prolongation of survival of critically-ill patients. Two other important factors, observed mainly in cancer patients, are colonization of mucous membranes by yeasts, and neutropenia, resulting from increased use of antibiotics and anti-neoplastic agents, respectively. The crude mortality rate of candidaemia is high (38-75%), and the attributable mortality has been estimated at 25-38%. During the past 15 years, the prevalence of infections caused by non-albicans Candida spp. has increased exponentially, so that these organisms now account for > 50% of episodes of fungaemia in various surveys. The increase in invasive fungal infections, the associated high mortality rate, and the emergence of antifungal resistance, have all driven the search for more potent antifungal drugs. The aims of the present study are to investigate the prevalence and the epidemiology of candidaemia and to determine the antifungal susceptibility patterns of Candida spp. isolates from a tertiary-care hospital in Italy.