View clinical trials related to Genetic Polymorphisms.
Filter by:Sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown further reductions in heart failure hospitalization, cardiovascular events, and mortality, especially for heart failure patients. The SGLT2 gene, also known as SLC5A2 (solute carrier family 5 member 2), is located on chromosome 16 and is responsible for encoding SGLT2. Several SLC5A2 mutations alter SGLT2 expression, membrane location, or transporter function. Several common genetic variations were found in the SLC5A2 gene that may affect the response to treatment with SGLT2 inhibitors.
The aim of study is to examine the relationship between lipid subfractions, inflammation and structural-functional properties of the arterial wall in patients after myocardial infarction with high lipoprotein (a) (Lp (a)) levels, to study genetic polymorphisms that determine lipid subfractions concentration on the functional and morphological properties of the arterial vascular wall in patients after myocardial infarction with high Lp (a) levels, to study the effect of pelacarsen on lipid subfractions, inflammation and structural-functional properties of arterial wall in patients after myocardial infarction with high Lp (a) levels and to study the influence of NOS-3 gene expression on the functional and morphological properties of the arterial vascular wall in the same patients. Impaired blood fat metabolism and chronic inflammation represent possible causes of atherosclerosis. Lp (a) is an independent risk factor for cardiovascular disease and a prognostic predictor in patients after myocardial infarction. Despite recommended screening for elevated Lp (a), there is no specific drug treatment approved to reduce cardiovascular risk through lowering Lp (a). Besides subtilisin-kexin convertase type 9 (PCSK9) inhibitors, antisense oligonucleotides (ASOs) are currently only therapeutic agents that significantly reduce serum Lp (a) concentration. Pelacarsen by using an ASO directed against the messenger ribonucleic acid (mRNA) of apolipoprotein (a), reduces the production of apolipoprotein (a) in the liver and thus, the level of Lp (a). However, there are no data on the relationship between Lp (a) values and polymorphisms for Lp (a), indicators of inflammation and impaired arterial function, and response to treatment with pelacarsen in patients after myocardial infarction with extremely high Lp (a) levels.
The aim of study is to examine the relationship between lipid subfractions, inflammation and structural-functional properties of the arterial wall in patients with premature coronary heart disease, to study genetic polymorphisms that determine lipid subfractions concentration on the functional and morphological properties of the arterial vascular wall in patients with early coronary heart disease, to study the effect of alirocumab and evolocumab on lipid subfractions, inflammation and structural-functional properties of arterial wall in patients with early coronary atherosclerosis and to study the influence of NOS-3 gene expression on the functional and morphological properties of the arterial vascular wall in the same patients. Impaired blood fat metabolism and chronic inflammation are intertwined as possible causes of atherosclerosis. Lipoprotein (a) (Lp (a)) is an important risk factor for coronary heart disease and a prognostic predictor in patients after myocardial infarction, but recent research suggests that subtilisin-kexin convertase type 9 (PCSK9) inhibitors are the only drugs that significantly reduce serum Lp (a) concentration. However, there are no data on the relationship between Lp (a) values and polymorphisms for Lp (a), indicators of inflammation and impaired arterial function, and response to treatment with various PCSK9 inhibitors in patients with early coronary heart disease.
Every year, more than 5 million patients in the US experience postoperative nausea and/or vomiting (PONV) and in the ambulatory setting post-discharge nausea and/or vomiting (PDNV) is the most common cause for unanticipated hospital re-admissions. Similarly, millions of patients suffer from chemotherapy induced nausea and/or vomiting (CINV), and one out of five patients discontinues chemotherapy for this reason. Thus, the control of nausea and vomiting remains a major health concern for the investigators society. The investigatorsoverall goal is to further the understanding of nausea and vomiting and optimize antiemetic selection in order to facilitate individualized patient care. Unfortunately, current antiemetics reduce the incidence of nausea by only about one third. As a result, antiemetics are often combined, exposing patients to adverse events and drug interactions without evidence for the most effective combination. Moreover, it remains unclear why such a large amount of inter-individual variability exists in antiemetic responsiveness. 5HT3, NK1, and GABA receptors are targets for some of the most commonly prescribed anti-emetics. Furthermore, these receptors have many known genetic polymorphisms, including several linked to incidence of nausea and vomiting. Thus pharmacogenomic variation may in part explain interindividual differences in treatment responses and will be tested in this proposal. Leveraging the established infrastructure of the UCSF Clinical and Translational Science Institute, and the support of 6 patient recruitment sites, the investigators will enroll 1280 high risk patients to three oral interventions with distinct mechanisms of action for nausea and vomiting. Investigating nausea and vomiting in ambulatory surgical patients is an excellent model for this trial owing to a high incidence, short observational period, and the ability to standardize and control potentially confounding variables. In this proposal, 100% of patients will receive a single intraoperative dose of 4 mg ondansetron, which is similar to the 80% of patients who receive prophylaxis in common practice. Using a factorial design, these patients will be randomized to receive one out of eight possible combinations of the three interventions (ondansetron, aprepitant, lorazepam) versus placebo (ond+aprep+lora, ond+aprep, ond+lora, aprep+lora, ond, aprep, lora, or placebo). Thus, in this proposal 87.5% (7 out of 8 patients) will have antiemetic coverage for the postdischarge period, which is considerably higher than in common practice, where only 4% of patients have antiemetic coverage after discharge. The primary endpoint will be the prevention of nausea and vomiting within 48 hours after ambulatory surgery. The advantage of the factorial trial design is its high efficiency to systematically investigate multiple interventions while allowing us to test for potential interactions. It is also an ideal format for the simultaneous assessment of pharmacogenomic interactions of antiemetics in this proposal. To this end, the investigators will collect DNA samples and take advantage of the unique opportunity to investigate the effects of variation in candidate receptor genes in the context of the three treatment interventions for PDNV. This approach may in part explain inter-individual differences in drug efficacy and allow for future screening of at-risk patients. Specifically, the investigators will be assessing single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) of targeted receptors for the antiemetics tested. Aim 1: To determine efficacy of three interventions for the prevention of PDNV. Hypothesis 1.1: Each intervention reduces the incidence of PDNV. Hypothesis 1.2: Efficacy of all interventions is independent so that efficacy of a combination can be derived from the efficacy of the individual interventions. Aim 2: To determine if drug response for anti-emetics is dependent upon genetic variance. Hypothesis 2: Efficacy of ondansetron, aprepitant and lorazepam to reduce PDNV differs with 5HT3, NK1, and GABA receptor gene variation, respectively.
The Environmental Genome Project (EGP) has completely or partially resequenced the protein coding and regulatory regions of 53 environmentally sensitive genes from 72 anonymous individuals of varying ethnic backgrounds to date. Some of the same genes have been resequenced in an additional set of 20 samples, and, in a subset of these, the introns and promoter regions have been sequenced as well. Within this population, 523 allelic variants (genetic polymorphisms), mostly single nucleotide polymorphisms (SNPs), have been found to date. If the polymorphism alters the behavior or expression of the encoded protein, it might be of clinical significance. The Office of Clinical Research is planning to establish a large resource bank of frozen DNA samples (20,000) and make it available to NIEHS intramural investigators involved in the EGP to screen for the presence of these SNPs and other mutations by standard genotyping methods. To investigate the feasibility of such a large collection of samples, we plan to first conduct a pilot study to estimate the accrual rate and uncover potential problems that may be encountered in the larger effort. This IRB proposal is for the pilot study in which we will collect whole blood samples (EDTA-anticoagulated) from 481 patients at UNC Medical Center. Once the pilot study is complete, we will decide whether to proceed with the larger, 20,000 sample collection and if so, develop and submit for review a new IRB protocol for its implementation taking date from the pilot study into account. For both the pilot study and larger, 20,000 sample collection, only blood left over from patients already having their blood drawn for hematology (complete blood count or CBC) assays as part of their routine clinical management will be used, thus eliminating the need to collect extra blood. Once the samples have been obtained from the clinical hematology laboratory and processed, they will be identifiable only with a unique identification number and sent to an NIEHS contractor (BioServe Biotechnlolgies, Laurel, MD) for DNA isolation. During recruitment, interviewers will explain the study to potential participants, obtain their signatures on the informed consent documents, and answer any questions they have concerning this study. At this time, potential participants will be informed that, depending on the results of the genetic analyses of their blood samples, they may be recontacted at a later date and asked to participate in follow-up genotype/phenotype studies. These follow-up studies will be separate from this protocol and the subjects of future IRB proposals. The ultimate objective of these sample collections, combined with the follow-up genotype/phenotype studies, is to identify groups of individuals with genetic polymorphisms in environmentally sensitive genes, and to correlate their genotype with their clinical phenotype, a process known as "ascertainment by genotype."