Search results for "pharmacogenetics."
showing 9 items of 79 documents
The role of polymorphisms of thiopurine methyltransferase in therapy with Azathioprine: preliminary study
2018
Azathioprine is an immunosuppressant drug belonging to the class of thiopurines widely used in clinical therapy. Its immunosuppressive action is linked to the substantial action mechanism in the inhibition of the synthesis of nitrogenous bases purine carried out in T-lymphocyte. The level of such medication limit resides in side effects such as myelosuppression and the development of tumours. The occurrence of side effects is linked to the presence of genetic polymorphisms of Thiopurine methyltransferase (TPMT). To date, 40 allelic variants for TPMT have been detected. However, those responsible for the reduction of enzyme activity are three: *2, *3A, *3C. The presence of one of the three p…
Molecular docking and pharmacogenomics of vinca alkaloids and their monomeric precursors, vindoline and catharanthine.
2011
International audience; Vinblastine and vincristine are dimeric indole alkaloids derived from (formerly: ). Their monomeric precursor molecules are vindoline and catharanthine. While vinblastine and vincristine are well-known mitotic spindle poisons, not much is known about vindoline and catharanthine. Vindoline and catharanthine showed weak cytotoxicity, while vinblastine, vincristine, and the semisynthetic vindesine and vinorelbine revealed high cytotoxicity towards cancer cells. This may reflect a general biological principle of poisonous plants. Highly toxic compounds are not only active towards predators, but also towards plant tissues. Hence, plants need mechanisms to protect themselv…
Pharmacogenomics in psychiatry: from therapeutic drug monitoring to genomic medicine.
2013
Psychiatry is increasingly combining new pharmacogenomic findings with therapeutic drug monitoring (TDM) to improve the safety and efficacy of pharmacotherapy. However, a distinction should be made between “nice to know” and “need to know” pharmacogenomic data because many results are statistically significant in meta-analyses but are not clinically relevant due to their low effect sizes. Some examples will illustrate this integration.
<i>PCSK9</i> rs11591147 R46L Loss-of-Function Variant Protects Against Liver Damage in Individuals with NAFLD
2020
Background and Aims: The proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in cholesterol homeostasis, and its inhibition represents an effective therapy to lower LDL-C levels. In this study, we examined the impact of PCSK9 rs11591147 loss-of-function (LOF) variant on liver damage in a multicenter collection of patients at risk of nonalcoholic steatohepatitis (NASH), in clinical samples and experimental models. Methods: We considered 1,874 consecutive individuals at risk of NASH as determined by histology. The SNP rs11591147, encoding for the p.R46L variant of PCSK9, was genotyped by TaqMan assays. We also evaluated 1) PCSK9 mRNA hepatic expression in human liver, and 2…
Pharmacogenetics and Pharmacotherapy of Military Personnel Suffering from Post-traumatic Stress Disorder
2017
Background Posttraumatic stress disorder (PTSD) is a severe problem among soldiers with combating experience difficult to treat. The pathogenesis is still not fully understood at the psychological level. Therefore, genetic research became a focus of interest. The identification of single nucleotide polymorphisms (SNPs) may help to predict, which persons are at high risk to develop PTSD as a starting point to develop novel targeted drugs for treatment. Methods We conducted a systematic review on SNPs in genes related to PTSD pathology and development of targeted pharmacological treatment options based on PubMed database searches. We focused on clinical trials with military personnel. Results…
Pharmacogenetics in Neuroblastoma: What Can Already Be Clinically Implemented and What Is Coming Next?
2021
Pharmacogenetics is one of the cornerstones of Personalized Precision Medicine that needs to be implemented in the routine of our patients’ clinical management in order to tailor their therapies as much as possible, with the aim of maximizing efficacy and minimizing toxicity. This is of great importance, especially in pediatric cancer and even more in complex malignancies such as neuroblastoma, where the rates of therapeutic success are still below those of many other types of tumors. The studies are mainly focused on germline genetic variants and in the present review, state of the art is presented: which are the variants that have a level of evidence high enough to be implemented in the c…
F9 missense mutations impairing factor IX activation are associated with pleiotropic plasma phenotypes.
2022
Background Circulating dysfunctional factor IX (FIX) might modulate distribution of infused FIX in hemophilia B (HB) patients. Recurrent substitutions at FIX activation sites (R191-R226, >300 patients) are associated with variable FIX activity and antigen (FIXag) levels. Objectives To investigate the (1) expression of a complete panel of missense mutations at FIX activation sites and (2) contribution of F9 genotypes on the FIX pharmacokinetics (PK). Methods We checked FIX activity and antigen and activity assays in plasma and after recombinant expression of FIX variants and performed an analysis of infused FIX PK parameters in patients (n = 30), mostly enrolled in the F9 Genotype and PK HB …
Review of Pharmacokinetics and Pharmacogenetics in Atypical Long-Acting Injectable Antipsychotics
2021
Over the last two decades, pharmacogenetics and pharmacokinetics have been increasingly used in clinical practice in Psychiatry due to the high variability regarding response and side effects of antipsychotic drugs. Specifically, long-acting injectable (LAI) antipsychotics have different pharmacokinetic profile than oral formulations due to their sustained release characteristics. In addition, most of these drugs are metabolized by CYP2D6, whose interindividual genetic variability results in different metabolizer status and, consequently, into different plasma concentrations of the drugs. In this context, there is consistent evidence which supports the use of therapeutic drug monitoring (TD…
Pharmacogenomics: A Step forward Precision Medicine in Childhood Asthma.
2022
Personalized medicine, an approach to care in which individual characteristics are used for targeting interventions and maximizing health outcomes, is rapidly becoming a reality for many diseases. Childhood asthma is a heterogeneous disease and many children have uncontrolled symptoms. Therefore, an individualized approach is needed for improving asthma outcomes in children. The rapidly evolving fields of genomics and pharmacogenomics may provide a way to achieve asthma control and reduce future risks in children with asthma. In particular, pharmacogenomics can provide tools for identifying novel molecular mechanisms and biomarkers to guide treatment. Emergent high-throughput technologies, …