Textbook of Personalized Medicine - Second Edition [2015]

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and the effi cacy for morphine in cancer pain treatment. Genetic variation in the
COMT gene can infl uence the effi cacy of morphine and can explain differences in
morphine requirements in individual cancer patients with pain (Rakvåg et al. 2008 ).
Although available evidence on individual genotype associations with pain, anal-
gesia and opioid adverse outcome are promising, confl icting data in the literature
indicates that there is a need for larger and more robust studies with appropriate popu-
lation stratifi cation and consideration of nongenetic and other genetic risk factors.
Relationships between perioperative pain relief in children by opioid drugs and four
common SNPs in the COMT gene have been by examined (Sadhasivam et al. 2014 ).
Minor allele carriers of each of these four COMT SNPs, which are predictive of lower
COMT activity, were 2.6–3.1 times more likely to require additional analgesic interven-
tions than children homozygotes for the major COMT alleles. These fi ndings may refl ect
higher CNS catecholamine levels that mediate increased pain sensitivity. This study sug-
gests that application of genotyping can improve surgical pain management in children.

Pharmacogenetics of NSAIDs

Relief of pain from different NSAIDs varies among patients. It is known that small
substitutions in the active site of COX-1, e.g., Ile (isoleucine) for Val (valine), pro-
duce the different active site found in COX-2. Therefore, small changes, be they
splice variants or mutations, may produce dramatic effects. Mutations such as these
might underlie the reason why different patients appear to prefer different NSAIDs.
No defi nite studies have been done on this topic but the phenomenon appears to be
widespread as products from approximately one-third of human genes undergo
alternative splicing. Different variants from the COX-1 and COX-2 genes could
underlie constitutive and inducible prostanoid production. Also, polymorphisms

Genetic factors

Non-genetic factors

Physiological Psychological Drug interactions

Efficacy & side effects of opioids

Race

Metabolizing

enzymes Transporters

Opioid

receptors

Signal

transduction

CYP2D6

UGT2B7 ABCB COMT, OPRM1, MC1R

Fig. 12.6 Genetic & non-genetic factors affecting effi cacy and side effects of opioids (Modifi ed
from Sadhasivam et al. 2014 )

12 Personalized Management of Neurological Disorders