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

Pharmacogenomics and Laboratory Medicine
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is to analyze the whole exome and whole genome sequence to assess interpatient
variability in drug response and side effects and discover novel targets for personalized
therapy. In recognition of the importance of pharmacogenomics and revolution
of personalized medicine, the Obama administration recently unveiled the Precision
Medicine Initiative to improve health and treat disease. * Pharmacogenomics will
shed light on producing more powerful drugs by targeting specific diseases with
maximized therapeutic effects and minimized side effects. Appropriate drug doses
will be determined by pharmacogenomics based on a patient’s genetic makeup in
addition to his or her body weight and age. In the near future, pharmacogenomics
will make the dream of precision medicine a reality.
STUDY QUESTIONS
1. What percentage of differences in drug efficacy and adverse effect is due to
genetics?
a. 5%
b. 10%
c. 20–95%
d. 100%
2. What are single nucleotide polymorphisms (SNPs)? How many SNPs are
there in human genomes?
3. How many metabolizer groups are in the CYP2D6 gene?
4. Give one example of a drug metabolized by thiopurine methyltransferase
(TPMT)?
5. What does a drug transporter do?
6. What is a Philadelphia chromosome? What is the fusion gene on a Ph
chromosome?
7. What is the gold standard test to detect ALK rearrangement?
8. List the two most common mutations in EGFR that are responsible for
about 90% of NSCLC cases?
9. Germline mutations of which genes cause hereditary breast–ovarian cancer
(HBOC) syndrome?
Answers
1. c
2. SNPs are the most common form of polymorphisms, defined as the occurrence
at an allele frequency of at least 1/1000 bases in the general population.
There are an estimated 1.4 million SNPs in the human genome.
3. Four. Poor metabolizer, intermediate metabolizer, ultrarapid metabolizer,
and extensive metabolizer.
4. 6-Mercaptopurine is used to treat acute lymphoblastic leukemia of
childhood.
5. To transport drug across the cell membrane.
* https://www.whitehouse.gov/the-press-office/2015/01/30/fact-sheet- president-obama-s-precisionmedicine-initiative