Nicotine is the primary addictive compound in tobacco smoke. In this review we summarize nicotine dependence and the genetics of smoking in brief before focusing on cytochrome P450 (CYP) 2A6. In humans nicotine is mainly inactivated to cotinine and CYP2A6 mediates approximately 90% of this conversion. Some, but not all, studies suggest that genetic variation in CYP2A6 may play a role in smoking. We review some of the recent findings on the influence of CYP2A6 genetic polymorphisms on nicotine kinetics, smoking behaviors, and how the gene appears to exert differential effects during various stages of smoking (eg, initiation, conversion to dependence, amount smoked during dependence, and quitting). These new findings will be put in the context of the discrepancies found in the literature. Implications of these recent findings on current and novel treatment approaches for smoking cessation and tobacco-related lung cancer will also be discussed.
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http://dx.doi.org/10.1016/j.clpt.2004.10.011 | DOI Listing |
Front Pharmacol
January 2025
Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong Province, China.
Purpose: The incidence of hemodynamic instability associated with dexmedetomidine (DEX) sedation has been reported to exceed 50%, with substantial inter-individual variability in response. Genetic factors have been suggested to contribute significantly to such variation. The aim of this study was to identify the clinical, pharmacokinetic, and genetic factors associated with DEX-induced hemodynamic instability in pediatric anesthesia patients.
View Article and Find Full Text PDFSci Rep
December 2024
National Biobank of Thailand, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani, Thailand.
Inter-individual variability in drug responses is significantly influenced by genetic factors, underscoring the importance of population-specific pharmacogenomic studies to optimize clinical outcomes. In this study, we analyzed whole genome sequencing data from 949 unrelated Thai individuals and conducted an in-depth analysis of 3239 genes involved in drug pharmacokinetics, pharmacodynamics, or immune-mediated adverse drug reactions. We identified 43 single nucleotide polymorphisms (SNPs), 134 diplotypes, and 15 human leukocyte antigen (HLA) alleles, all with moderate to high clinical significance.
View Article and Find Full Text PDFBMC Pulm Med
December 2024
Department of Integrative Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Background: Chronic obstructive pulmonary disease (COPD) is closely linked to lung cancer (LC) development. The aim of this study is to identify the genetic and clinical risk factors for LC risk in COPD, according to which the prediction model for LC in COPD was constructed.
Methods: This is a case-control study in which patientis with COPD + LC as the case group, patientis with only COPD as the control group, and patientis with only LC as the second control group.
Nicotine Tob Res
December 2024
Department of Public Health, Medical University of South Carolina, Charleston SC.
Introduction: Genetic studies of smoking cessation have been limited by short-term follow-up or cross-sectional design. Within seven genes (CHRNA3, CHRNA5, CHRNB2, CHRNB4, DRD2, DBH and CYP2A6) influencing biological mechanisms relevant to smoking, this study aimed to identify single nucleotide polymorphisms (SNPs) associated with smoking cessation throughout up to 38-years of follow-up.
Methods: Participants were from two all-female cohort studies, Nurses' Health Study (NHS) (n = 10,017) and NHS-2 (n = 2,793).
Clin Transl Sci
December 2024
Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Dexmedetomidine is a centrally acting alpha-2 agonist used for initiation and maintenance of procedural sedation and mechanical ventilation in adult and pediatric settings. It is commonly used in both pediatric and neonatal intensive care units. Dexmedetomidine requires extensive titration, and patients can be over or under-sedated during titration, leading to adverse events such as hypotension and bradycardia, or inadequate sedation, which can result in self-extubation.
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