Pharmacogenetics of drug dependence: role of gene variations in susceptibility and treatment.

  title={Pharmacogenetics of drug dependence: role of gene variations in susceptibility and treatment.},
  author={Jibran Younis Khokhar and Charmaine S. Ferguson and Andy Z. X. Zhu and Rachel F. Tyndale},
  journal={Annual review of pharmacology and toxicology},
Drug dependency is a highly prevalent mental health disorder that imposes a significant burden on those directly affected, health care systems, and society in general. There is substantial heritability in the susceptibility to drug addiction, which indicates that there are genetic risk factors. Variation in the human genome is abundant and can directly affect drug dependency phenotypes, for example, by altering the function of a gene product or by altering gene expression. Pharmacogenetic… 

Breaking Barriers in the Genomics and Pharmacogenetics of Drug Addiction

There is growing evidence that genetic information can be useful in refining the choice of addiction treatment and as genetic testing becomes more common in the practice of medicine, a variety of ethical and practical challenges will also need to be considered.

ALDH5A1 variability in opioid dependent patients could influence response to methadone treatment

Cytochrome P450-mediated drug metabolism in the brain.

Advancing knowledge of brain CYP-mediated metabolism may help to understand why patients respond differently to drugs used in psychiatry and predict risk for psychiatric disorders, including neurodegenerative diseases and substance abuse.

The genetic aspects of nicotine metabolism and their impact on adolescent nicotine dependence

Variation in nicotine metabolism assists in understandi ng variability in response to nicotine and liability to smok ing, providing the potential of identifying individuals at greater risk of smoking, sustained smoking and smoking related disorders and also may assist in personalizing treatment to improve efficacy of nicotine replacement therapies.

Opioid Dependence Risk Factors and Risk Assessment

Reduction of individual- and population-level opioid dependence will require adaptation of the host(s) if the opioid epidemic is to be contained and reversed. Attempts to alter abuse liability of

The genetic basis of delay discounting and its genetic relationship to alcohol dependence

Pharmacogenomics: A Promising Approach Towards Treatment of Autism

Recent developments of genetics and pharmacogenomics in the field of autism are described and the prospective of pharmacogenetics in developing novel and more effective therapies, and personalizing treatment strategies for autism is highlighted.


It will be thus difficult to ensure that the considerable economic costs associated with the development of tailored medicine for a minority that shares genetic similarities are in balance with the equitable treatment for anyone, regardless of race.

An Investigation of CYP2B in Rat Brain: Regulation and Role in Drug and Toxin Response

Induction of CYP2B in rat brain, by chronic nicotine treatment, reduced the anaesthetic efficacy of propofol, through increased brain CYP1Bmediated metabolic inactivation and inhibition of brain CYp2B, using mechanism based inhibitors of the enzyme.



Symbiotic relationship of pharmacogenetics and drugs of abuse

  • J. Rutter
  • Biology, Medicine
    The AAPS Journal
  • 2008
This review highlights key studies and identifies important genes in drug abuse pharmacogenetics that provide a basis for better diagnosis and treatment of drug abuse disorders.

Molecular Biology of Alcohol Dependence, a Complex Polygenic Disorder

Designs which include related subjects have advantages for the study of complex diseases, because any association effects can be placed in the context of overall heritability and because linkage analysis can also be included.

Twin studies of psychiatric illness: an update.

  • K. Kendler
  • Psychology
    Archives of general psychiatry
  • 2001
The studies reviewed suggest that (1) the heritability of many behavioral traits may be greater in permissive than in restrictive environments and (2) for psychiatric and drug abuse disorders, genes probably work through both traditional within-the-skin physiological pathways and outside- the-skin behavioral pathways.

Pharmacogenetics and Human Molecular Genetics of Opiate and Cocaine Addictions and Their Treatments

The molecular genetics and pharmacogenetics of opiate and cocaine addictions are reviewed, focusing primarily on genes of the opioid and monoaminergic systems that have been associated with or have evidence for linkage to opiate or cocaine addiction.

Genetic variation in the CHRNA5 gene affects mRNA levels and is associated with risk for alcohol dependence

It is observed that a different group of polymorphisms, spanning CHRNA5-CHRNA3, demonstrate association with alcohol dependence defined by Diagnostic and Statistical Manual of Mental Disorders, 4th edn (DSM-IV) criteria.

Overview of the pharmacogenomics of cigarette smoking

This paper reviews the current state of knowledge for genetic factors implicated in smoking behaviors, and examines how genetic variations may affect therapeutic outcomes for drugs used to assist smoking cessation.

[Alcohol dependence and polymorphisms of serotonin-related genes].

Genes involved in the transmission, reuptake and metabolism of serotonin constitute a set of candidate genes that could be involved in core aspects of alcoholism, such as the tendency to prefer immediate reward, despite negative consequences.

Chromosome 15q25.1 genetic markers associated with level of response to alcohol in humans

It is shown that two of the markers from the nicotine studies also show an association with several LR phenotypes in a sample of 367 siblings, indicating that LR intermediate phenotypes have utility in genetic approaches toAUDs and will prove valuable in the identification of other genetic loci conferring susceptibility to AUDs.

Pharmacogenetics of responses to alcohol and genes that influence alcohol drinking.

  • T. Li
  • Medicine
    Journal of studies on alcohol
  • 2000
Results from studies qualifying alcoholism as a pharmacogenetic disorder of the brain are presented, finding that there are genetic predisposing factors for alcoholism.

Allelic and haplotypic association of GABRA2 with alcohol dependence

Ten single nucleotide polymorphisms spanning the coding region of this gene were examined in samples of European American subjects with alcohol dependence, and controls screened to exclude substance use disorders, which underscore the potential contribution of polymorphic variation at the GABRA2 locus to the risk for alcohol dependence.