Pharmacogenetics and genomics
-
Pharmacogenet. Genomics · Aug 2018
Genetic polymorphisms in candidate genes are not associated with increased vincristine-related peripheral neuropathy in Arab children treated for acute childhood leukemia: a single institution study.
The aim of this study was to evaluate the potential association between candidate genetic polymorphisms and vincristine-related peripheral neuropathy in Arab children with acute lymphoblastic leukemia (ALL). ⋯ This study presents the first pharmacogenetic analysis of vincristine-related peripheral neuropathy in children with ALL in an Arab country. We have shown that genetic polymorphisms in candidate genes are not associated with peripheral neuropathy secondary to chronic therapy with high-dose vincristine (2 mg/m) during the continuation phase. Concerning CEP72, our results are in line with the findings from the St Jude cohort of children treated for ALL with higher vincristine doses during chronic treatment. Larger high-throughput genetic analyses may be warranted to evaluate variants in other candidate genes such as CYP3A5 and reveal new nonpreviously reported alleles that may be peculiar to this region of the world.
-
Pharmacogenet. Genomics · May 2017
Impact of the CYP2C19 genotype on voriconazole exposure in adults with invasive fungal infections.
Voriconazole, a first-line agent for the treatment of invasive fungal infections (IFIs), is metabolized by CYP2C19. A significant proportion of patients fail to achieve therapeutic trough concentrations with standard weight-based voriconazole dosing, placing them at increased risk for treatment failure, which can be life threatening. We sought to test the association between the CYP2C19 genotype and subtherapeutic voriconazole concentrations in adults with IFIs. ⋯ Our findings indicate that adults with the CYP2C19 RM or UM phenotype are more likely to have subtherapeutic concentrations with weight-based voriconazole dosing. These results corroborate previous findings in children and support the potential clinical utility of CYP2C19 genotype-guided voriconazole dosing to avoid underexposure in RMs and UMs.
-
Pharmacogenet. Genomics · Aug 2016
CYP2D6 function moderates the pharmacokinetics and pharmacodynamics of 3,4-methylene-dioxymethamphetamine in a controlled study in healthy individuals.
The role of genetic polymorphisms in cytochrome (CYP) 2D6 involved in the metabolism of 3,4-methylene-dioxymethamphetamine (MDMA, ecstasy) is unclear. Effects of genetic variants in CYP2D6 on the pharmacokinetics and pharmacodynamic effects of MDMA were characterized in 139 healthy individuals (70 men, 69 women) in a pooled analysis of eight double-blind, placebo-controlled crossover studies. ⋯ Blood pressure and subjective drug effects increased more rapidly after MDMA administration in poor metabolizers than in extensive metabolizers. In conclusion, the disposition of MDMA and its effects in humans are altered by polymorphic CYP2D6 activity, but the effects are small because of the autoinhibition of CYP2D6.
-
Pharmacogenet. Genomics · Jul 2016
Patients with prolonged effect of succinylcholine or mivacurium had novel mutations in the butyrylcholinesterase gene.
Mutations in the butyrylcholinesterase enzyme (BChE) can result in prolonged duration of action of the neuromuscular blocking agents, succinylcholine and mivacurium, as BChE hydrolyses these drugs. Hereditary low BChE activity can cause extensively prolonged apnoea during general anaesthesia when these drugs are used. The aim of this study was to describe novel mutations in the butyrylcholinesterase gene (BCHE) in patients who have experienced prolonged duration of action of mivacurium or succinylcholine. ⋯ We have found seven new variants of the BCHE, which seem to reduce the activity of BChE in patients undergoing anaesthesia involving succinylcholine or mivacurium.
-
Pharmacogenet. Genomics · Feb 2016
Lack of association of the CEP72 rs924607 TT genotype with vincristine-related peripheral neuropathy during the early phase of pediatric acute lymphoblastic leukemia treatment in a Spanish population.
Vincristine is a component of acute lymphoblastic leukemia (ALL) treatment with the potential to induce peripheral neuropathy. Recently, the CEP72 rs924607 TT genotype was found to be associated with vincristine-induced toxicity during the continuation phase in pediatric ALL patients treated on the Total XIIIB and COG AALL0433 protocols at St Jude Children's Research Hospital and Children's Oncology Group. This finding could provide a base for safer dosing of vincristine. ⋯ Therefore, the aim of this study was to determine whether the CEP72 rs924607 TT genotype is a useful marker of vincristine neuropathy during induction therapy among Spanish children with B-ALL treated on the LAL-SHOP protocols. No association was found between neurotoxicity during the induction phase and the rs924607 TT genotype. This lack of association could be because of population differences and/or differences in neurotoxicity etiology between induction and continuation phases of treatment.