Feng, Xiaodong_ Xie, Hong-Guang - Applying pharmacogenomics in therapeutics-CRC Press (2016)

214 Applying Pharmacogenomics in Therapeutics
in more frequent motor complications of long-term l-Dopa use; associations
of late-onset hallucinations with the C allele of the taq1A polymorphism
10.5 kb of DRD2; and similar results obtained in DRD1, DRD2, DRD3, and
DRD4 in patients with PD with or without chronic visual hallucinations).
• COMT inhibitors with COMT and glucuronosyltransferase (UGT)1A9
(COMT haplotype appears to have little influence on the development of
l-Dopa-induced dyskinesias).
• Selegiline with CYP2B6 (CYP2B6*18 and other CYP2B6 defect variant
alleles may be potential biomarkers for altered selegiline biodisposition;
currently, there are no recommendations for selegiline use and CYP2B6
pharmacogenetics).
• Pramipexole with DRD3 [no significant associations between DRD3 (MscI
polymorphism) and DRD4 (120 bp tandem duplication polymorphism in the
promoter region)] polymorphisms and the phenomenon of “sleep attacks.” 57
PHARMACOGENOMICS OF ALCOHOL, NICOTINE,
AND DRUG ADDICTION TREATMENTS
One of the most promising areas of research in pharmacogenomics and addiction
treatment is the μ opioid receptor gene, OPRM1 A118G (rs561720) polymorphism.
Three randomized, placebo-controlled studies have shown that individuals with
a G allele display longer abstinence and greater reduction in the positive effects
of alcohol when taking naltrexone. 58–60 Additional studies are needed to test and
develop adaptive approaches to treatment based on genotype information. 61
The most encouraging pharmacogenetic data for smoking cessation treatment
relates to CYP2A6 polymorphisms. Two open-label studies of approximately 500
European subjects each found a link between nicotine metabolism and the effectiveness
of nicotine replacement therapy. CYP2A6 rapid metabolizers were less likely to
achieve abstinence with transdermal nicotine replacement. 62,63
Key Points: Further research is needed to determine how genetic information
in the treatment of addiction disorders will be incorporated into clinical practice
given the controversy regarding the implementation of genetic testing for complex
phenotypes. Prospective studies and pragmatic clinical trials evaluating the
use of genetic testing in a clinical setting and the effect on treatment outcome
are warranted to further evaluate prospective testing in addiction medicine prior
to implementation. 64
CONCLUSIONS AND FUTURE PERSPECTIVES
With the increasing number of medications used to treat all of the varying disorders
of the CNS, prescribing the correct medications for each patient will become
increasingly more difficult. There are numerous genetic factors that contribute to
the CNS disorders and many more which may ultimately lead to response or failure