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

Pharmacogenomics and Laboratory Medicine
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and applies into clinical practice of the genetic variants affecting drug metabolism,
transport, molecular targets/pathway, and genetic susceptibility to diseases. The US
Food and Drug Administration (FDA) defines pharmacogenomics (PGx) as “the
study of variations of DNA and RNA characteristics as related to drug response”
and pharmacogenetics (PGt) as “a subset of pharmacogenomics (PGx)” and “the
study of variations in DNA sequence as related to drug response.” * However, pharmacogenomics
and pharmacogenetics are used interchangeably at most times. The
ultimate goal of pharmacogenetics/pharmacogenomics is to improve drug safety and
efficacy by applying the right drug to the right patient with the right dose at the right
time, which is also known as personalized medicine (Hamburg and Collins 2010).
Realization of this goal of precision medicine requires collaborative efforts from
physicians, pharmacists, and staff working in laboratory medicine.
Laboratory medicine is the practice of a medical laboratory or clinical laboratory
to perform tests on clinical specimens to obtain information that helps the diagnosis,
treatment, and prevention of the disease. There are many fields of laboratory medicine,
including chemistry, cytology, hematology, histology, pathology, and genetics.
Dependent on the practical purpose, genetic testing can be diagnostic, prenatal,
presymptomatic, predispositional, and pharmacogenetic. Genetic testing should be
ordered by adequately trained healthcare providers who can give appropriate pretest
and posttest counseling and also performed in a qualified laboratory. Appropriate
laboratory should have Clinical Laboratory Improvement Amendments of 1988
(CLIA) certification and/or a necessary state license if required by the state where the
healthcare providers perform the testing. CLIAs are federal regulatory standards that
apply to all clinical laboratories testing performed on humans in the United States.
An objective of the CLIA is to ensure quality laboratory testing, including accuracy,
reliability, and timeliness of test results across all US facilities or sites that test human
specimens for medical assessment or diagnosis, and treatment or prevention of the
disease. Genetic testing laboratory personnel should be certified by the appropriate
accrediting agency. The laboratory director should be an MD or PhD who is credentialed
by the American Board of Medical Genetics (ABMG, now American Board of
Medical Genetics and Genomics, ABMGG). Both the states New York and California
also have specific credential requirements for a director of the genetic testing laboratory,
respectively. Laboratory staff, such as technologists, are usually credentialed by
the American Society of Clinical Pathology (ASCP). Genetic testing laboratories may
also have genetic counselors certified by the American Board of Genetic Counseling,
Inc. (ABGC) to provide pretest and posttest counseling.
Genetic variations affecting interindividual differences in drug response and
safety could be sequence alterations in genes encoding drug-metabolizing enzymes,
drug transporters, or drug targets. Drug-metabolizing enzymes catalyze many different
types of chemical processes, including oxidation, hydroxylation, and hydrolysis,
as well as conjugation reactions, such as acetylation, glucuronidation, or sulfation.
Examples of drug-metabolizing enzymes include the cytochrome P450 (CYP)
superfamily, N-acetyltransferases (NAT), UDP-glucuronosyltransferases (UGT),
* http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/
ucm073162.pdf