Textbook of Personalized Medicine - Second Edition [2015]

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Corporation offers a kinase SNP discovery program for customized polymorphism
mapping of human kinase genes. Amplicon modeling, primer design and assay vali-
dation have been established for over 1,600 amplicons within 92 different kinase
genes. Assays have been extensively optimized to provide high pass rates, low back-
ground, and informative results in GC rich regions. Kinase mutation mapping can
be used to pinpoint responder populations and facilitate the development of person-
alized medicine.

Effect of Genetic Polymorphisms on Disease Response to Drugs

Genetic polymorphism of genes and gene products may infl uence the disease-
modifying effects of drugs. DMET™ Plus biomarker panel (Affymetrix) enables
genotyping of the largest and most comprehensive set of key functional drug

Table 4.5 Polymorphisms in drug target genes that can infl uence drug response

Gene or gene product Drug Effects
ACE ACE inhibitors Renoprotective effects, blood-pressure
reduction, reduction in left ventricular
mass, endothelial function
Fluvastatin Reductions in low-density lipoprotein
cholesterol and apolipoprotein B
Progression or regression of coronary
atherosclerosis
Arachidonate
5-lipoxygenase

Leukotriene inhibitors Improvement in FEV 1

β 2 -Adrenergic
receptor

β 2 agonists Bronchodilatation, susceptibility to
agonist-induced desensitization,
cardiovascular effects
Bradykinin B2
receptor

ACE inhibitors ACE-inhibitor–induced cough

Dopamine receptors
(D2, D3, D4)

Antipsychotics Antipsychotic response (D2, D3, D4),
antipsychotic-induced tardive
dyskinesia (D3), antipsychotic-induced
acute akathisia (D3)
Estrogen receptor Conjugated estrogens
Hormone-replacement

Increase in bone mineral density
Increase in high-density lipoprotein
cholesterol
Glycoprotein IIIa
subunit of
glycoprotein IIb/
IIIa

Aspirin or glycoprotein

IIb/IIIa inhibitors

Antiplatelet effect

Serotonin (5-HT)
transporter

Antidepressants 5-Hydroxytryptamine neurotransmission,
antidepressant response
Tyrosine kinase Imatinib mesylate
(Gleevec) for chronic
myeloid leukemia

A mutation in the Abl kinase domain of the
Bcr-Abl gene may produce
drug-resistance
© Jain PharmaBiotech

4 Pharmacogenetics