Textbook of Personalized Medicine - Second Edition [2015]

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metabolism alleles within a single panel. The DMET Plus biomarker panel contains
biomarkers in all FDA-validated genes and covers more than 90 % of the current
ADME Core biomarkers as defi ned by the PharmaADME group. It offers 1,936
high value, biologically relevant markers in 225 drug metabolism enzyme, trans-
porter, and transferase genes. Together these features make the Affymetrix DMET
panel the most comprehensive one targeting all functional variants within drug
metabolism genes.
Some examples of genetic polymorphisms are shown in Table 4.6. Such informa-
tion is useful in identifying the responders to drugs and is discussed further in sub-
sequent chapters.

Ethnic Differences in Drug Metabolism

Ethnic differences in drug metabolism are well documented for a number of drugs.
The molecular mechanisms responsible for ethnic differences in drug metabolism
have been partly clarifi ed because of the advances in molecular biology. Genotype
analysis indicates a different frequency for the mutant alleles in different ethnic
populations, which results in variations in the frequency of subjects who are homo-
zygous for the mutant allele among the extensive metabolizers in different ethnic
populations. Ethnic differences in drug metabolism may result from differences in
distribution of a polymorphic trait and mutations, which code for enzymes with
abnormal activity which occur with altered frequency in different ethnic groups.

Table 4.6 Effect of genetic polymorphisms on disease response to drugs

Gene or gene product Drug

Infl uence of polymorphism on disease
response to drug
Adducin Diuretics Decreased myocardial infarction in
hypertensive patients
Apolipoprotein E (APOE) Statins Reduction of progression of
atherosclerosis and enhanced
survival
Cholesterol ester transfer
protein (CETP)

Statins Slowing of progression of
atherosclerosis
Gs protein α β-blockers (e.g.,
metoprolol)

Decreased antihypertensive effect

Methylguanine methyl
transferase (MGMT)

Carmustine Enhanced response of glioblastoma to
carmustine
Parkin Levodopa Clinical improvement in Parkinson’s
disease
Serotonin transporter
(5-HTT)

Antidepressants (e.g.,

fl uoxetine)

Decreased clozapine effects,
antidepressant response
Stromelysin-1 Statins Reduction in cardiovascular events
and repeated angioplasty
© Jain PharmaBiotech

Role of Pharmacogenetics in Pharmaceutical Industry