AUG 21, 2013 8:00 AM PDT

Clinical Applications in Pharmacogenetics

C.E. Credits: CE
Speaker
  • Co-director, Pharmacogenomics and Genetics Laboratory, Co-director, Cardiovascular Laboratory Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic
    Biography
      Dr. Baudhuin is Assistant Professor of Laboratory Medicine and Pathology, with a joint appointment in the Department of Medical Genetics, at the Mayo Clinic in Rochester, MN. Dr. Baudhuin is a co-director of molecular genetics, pharmacogenetics, and cardiovascular testing laboratories at the Mayo Clinic. Dr. Baudhuin received her Ph.D. in Clinical Chemistry from Cleveland State University (in conjunction with the Cleveland Clinic) and followed that up with fellowship training in Clinical Chemistry and Clinical Molecular Genetics at the Mayo Clinic. Dr. Baudhuin is board certified in Clinical Molecular Genetics by the American Board of Medical Genetics. Dr. Baudhuin's research interests lie primarily in the areas of cardiovascular-related genetics and pharmacogenetics. Dr. Baudhuin was the recipient of the 2011 Outstanding Scientific Achievements by a Young Investigator (American Association for Clinical Chemistry); the 2010 Clinical Laboratory Sciences Distinguished Author Award (American Society of Clinical Laboratory Science); and the 2006 George Grannis Award for Excellence in Research and Scientific Publication (National Academy of Clinical Biochemistry).

    Abstract

    As a component of individualized medicine, pharmacogenetics (PGx) focuses on how genetic factors influence individual responses to specific medications. The clinical goals of pharmacogenetics are to identify the right drug at the right dose for each patient. The majority of known PGx-related variability is due to variation in genes encoding drug metabolizing enzymes. Variable drug metabolism can result in adverse drug events, ineffective therapies, and noncompliance with therapy. Pharmacogenetic variability can also be due to genetic variation in genes encoding drug transporters, drug targets, and proteins involved in immune response. Drugs with known pharmacogenetic variability may be labeled with PGx-related information. One example is clopidogrel which was updated in March 2010 by the FDA to contain information regarding response to clopidogrel in cytochrome P450 2C19 (CYP2C19) poor metabolizers. It has been demonstrated that individuals with reduced function CYP2C19 alleles do not effectively convert clopidogrel to its active metabolite, and this is associated with an increased rate of subsequent cardiovascular events and death. Other examples of pharmacogenetic-related drug labeling include warfarin and CYP2C9 and VKORC1 variation, psychiatric medications and CYP2C19/CYP2C9/CYP2D6 variation, thiopurines and TPMT variation, hypersensitivy to carbamazepine and abacavir due to HLA-B variation, and irinotecan and UGT1A1 variation. These and other examples are the basis for different clinical applications in pharmacogenetics with the ultimate goal of utilizing genetic information to determine the appropriate drug and dose for each patient.


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