Pharmacogenetics and genomics
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Pharmacogenet. Genomics · Apr 2014
Meta AnalysisCHRNA3 and CYP3A5*3 genotype, lung function and chronic obstructive pulmonary disease in the general population.
Genetic variations are most likely an additional risk factor besides tobacco smoking per se for the risk of chronic obstructive pulmonary disease (COPD). In this study, we compared genetic variants influencing the effect of smoking on COPD, that is, the effect of the well-known splicing defect polymorphism, CYP3A5*3 (rs776746), identified before genome-wide association studies, with the genome-wide association studies identified CHRNA3 (rs1051730) polymorphism on the risk of decreased lung function and COPD. ⋯ The CHRNA3 genotype is associated with decreased lung function and risk of COPD among ever-smokers, whereas this was not the case for CYP3A5*3.
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Pharmacogenet. Genomics · Jan 2014
Influence of ABCB1 and CYP3A5 genetic polymorphisms on the pharmacokinetics of quetiapine in healthy volunteers.
Quetiapine is an atypical antipsychotic drug used to treat schizophrenia and acute episodes of mania. Quetiapine is metabolized by CYP3A enzymes including CYP3A5 and is a substrate of P-glycoprotein, an efflux drug transporter encoded by the ABCB1 gene. We assessed the effects of ABCB1 [c.1236C>T (rs1128503), c.2677G>T/A (rs2032582), c.3435C>T (rs1045642)] and CYP3A5*3 (6986A>G) (rs776746) polymorphisms on the pharmacokinetics of quetiapine in humans. ⋯ The results indicated that the genetic polymorphism of CYP3A5*3 but not ABCB1 significantly influences the plasma level of quetiapine and its pharmacokinetics. These findings suggest that the CYP3A5 genetic polymorphism affects the disposition of quetiapine and provide a plausible explanation for interindividual variation in the disposition of this drug.
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Pharmacogenet. Genomics · May 2013
Expression of mRNA transcripts encoding membrane transporters detected with whole transcriptome sequencing of human brain and liver.
Membrane transporters control the influx and efflux of endogenous and xenobiotic substrates, including nutrients and drugs, across cellular membranes. ⋯ The results obtained with RNAseq provide detailed information on transporter mRNA expression at the molecular level, affording new avenues for the study of membrane transport, with relevance to drug efficacy and toxicity.
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Pharmacogenet. Genomics · Apr 2013
Genetic variation-optimized treatment benefit of angiotensin-converting enzyme inhibitors in patients with stable coronary artery disease: a 12-year follow-up study.
The objective of this study was to examine the relationship between renin-angiotensin system genotypes and the pharmacogenetics of angiotensin-converting enzyme (ACE) inhibitors in Chinese patients with coronary artery disease (CAD). ⋯ ACE inhibitors were associated with a significant decrease in MACE in Chinese patients diagnosed with CAD. Genetic variants were also associated with event-free survival, but their effects were modified by the use of ACE inhibitors.
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Pharmacogenet. Genomics · Apr 2013
The MAD1 1673 G → A polymorphism alters the function of the mitotic spindle assembly checkpoint and is associated with a worse response to induction chemotherapy and sensitivity to treatment in patients with advanced epithelial ovarian cancer.
Mitotic arrest deficient 1 (MAD1), a protein of the mitotic spindle assembly checkpoint (SAC), recognizes MAD2 through two leucine zippers, transporting and activating MAD2, which promotes a metaphase arrest signal. A single nucleotide polymorphism of MAD1 was found to affect the SAC function that could be involved in a poor response to therapeutic agents that alter the dynamics of microtubules. ⋯ The polymorphism MAD1 1673 G → A affects SAC functionality, increasing the frequency of aneuploid cells. This polymorphism modifies the response to agents that alter the dynamics of microtubules in patients with ovarian cancer.