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

Pharmacogenomics of CNS Disorder Treatments
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Key Points: Larger population confirmation studies are still needed on polymorphisms
in genes of the cholinergic markers that have been found to predict
better response to AChEIs: AChE, butyrylcholinesterase, choline AChE, and
paraoxonase. 47
EPILEPSY
Little evidence currently exists to correlate any CYP450 polymorphisms with clinical
response, serum drug concentrations, or other measurable outcomes in those
taking antiepileptic medications. Phenytoin metabolism is the only anticonvulsant
with evidence to suggest that variation in based on various CYP2C9 alleles can be
predictive of toxicity. 48,49
Recent research has shown that the human leukocyte antigen (HLA) HLA-B*1502
shows a strong association with carbamazepine-induced Stevens–Johnson syndrome
(SJS) in Han Chinese. 50 However, this association was not found in any Caucasian
populations. These findings did prompt the US FDA to change the labeling information
of carbamazepine to include information about HLA-B*1502, and the US FDA
now recommends genotyping individuals of Asian ancestry for the allele prior to
using the drug. 51
Key Points: HLA-B*1502 should be genotyped prior to initiation of carbamazepine
in the Asian ancestry population.
MULTIPLE SCLEROSIS
Candidate genes for HLA and interferon receptor polymorphisms have been studied
to determine response to therapy with inconsistent definitions of response and
markers studied. The HLA studies demonstrated that allelic variation has a correlation
with antibody production, but not with treatment response. 52,53 Interferon
receptor studies have demonstrated conflicting results. 53–55 One completed GWAS
found some promising results but was limited by only examining SNPs detected by
the author’s microarray. 55,56
PARKINSON DISEASE
Genetic variability, to some extent, is involved in the interindividual variability seen
with the response to drug treatments with Parkinson disease (PD). Although clinical
relevance has not been conclusively determined, there are interesting associations
between pharmacotherapy and genetic polymorphisms for the following pairs:
• l-Dopa with COMT and dopamine receptors (a SNP at nucleotide 1947
that encodes for low or high activity genotype is associated with changes in
response to both tolcapone and l-Dopa; DRD2 gene may play a pivotal role