475personalized treatment option. New treatment strategies focusing on genes contribut-
ing to drug and alcohol dependence (such as gene therapy) have been examined in
animal models and clinical trials have been conducted with drugs. Table 13.4 shows
genetic infl uences on pharmacotherapy of alcohol.
However, further research is required before these developments will consider-
ably change today’s clinical handling of alcoholism on an individual basis. The
NIH/ National Institute on Alcohol Abuse and Alcoholism (NIAAAA) is supporting
research in this area. Various human and animal studies can help to determine the
full range of genetic variation affecting the pharmacodynamic and pharmacokinetic
parameters that result in altered drug effi cacy and toxicity. Sequencing technologies
to identify variations in candidate genes that may play a role in drug responses, use
of pharmacogenetic testing to examine genetic variability in side effects from medi-
cation, and use of gene expression profi ling to determine transcriptomics changes
associated with drug response.
Personalized Therapy for Smoking Cessation
The evidence to date is very consistent with respect to the signifi cance of genetic
contributions to smoking behavior. Variants in the genes encoding the α5-α3-β4 nico-
tinic receptor subunits most strongly contribute to differences in the risk for develop-
ing nicotine dependence among smokers and a differential response to pharmacologic
treatment for smoking cessation (Bierut et al. 2014 ). As the fi eld of genetics and
smoking research progresses, increasing attention is being devoted to gene-environ-
ment interactions, with particular attention to the identifi cation of genetic variants
that may modify the effects of pharmacological treatment for smoking.
Table 13.4 Genetic infl uences on pharmacotherapy of alcoholismDrug Genetic variant Effect on outcome References
Topiramate GRIK1 (rs2832407) Heavy drinking days Kranzler et al. ( 2014 )
Adverse events
Naltrexone OPRM1 (Asn40Asp), DRD4
VNTR (rs1799971)
Heavy drinking days Kim et al. ( 2009 )
Abstinence rates
Relapse to heavy drinking
Ondansetron LL/LS/SS (5-HTTLPR)
(rs1042173), SLC6A4
(5-HTTLPR)
Drinks per drinking day Johnson et al. ( 2011 )
Days abstinentSertraline 5-HTTLPR triallelic SLC6A4 Heavy drinking days Kranzler et al. ( 2011 )
Drinking days
Acamprosate GATA4 (rs1327367) Relapse Kiefer et al. ( 2011 )
Disulfi ram DBH (rs161115) Adverse events Mutschler et al. ( 2012 )
Modifi ed from: Batki and Pennington ( 2014 )
Personalized Approach to Addiction