Loss-of-function CYP2C9 variants: finding the correct clinical role for Type 2 diabetes pharmacogenetic testing.
Continuing advances in genetic discovery have uncovered several dozen loci that are associated with Type 2 diabetes, including genetic variants that appear to modify responses to commonly prescribed diabetes medications. The use of an individual's genetic information to guide therapy choices raises the possibility of 'personalized medicine', wherein each patient's treatment plan is tailored based on genotype results. However, before such a model of care can be implemented, research is needed to more clearly quantify the association of genetic variation with treatment outcomes and adverse effects. In this article, we review a study examining the association of genetic variation in the cytochrome P450 2C9 enzyme with glycemic response to sulfonylureas in a large cohort of patients with Type 2 diabetes from the Genetics of Diabetes Audit and Research Tayside Study (Go-DARTS).
Grant
Richard W
RW
Division of General Medicine, Massachusetts General Hospital and Harvard Medical School, 50-59 Staniford Street, Boston, MA 02114, USA. rgrant@partners.org
Wexler
Deborah J
DJ
D000368:Aged; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001786:Blood Glucose / Q000187:drug effects / Q000235:genetics; D015331:Cohort Studies; D016001:Confidence Intervals; D065729:Cytochrome P-450 CYP2C9; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D010641:Phenotype; D011336:Probability; D016016:Proportional Hazards Models; D012016:Reference Values; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D016896:Treatment Outcome
D001786:Blood Glucose; D013453:Sulfonylurea Compounds; C400322:cytochrome P-450 CYP2C subfamily; D003577:Cytochrome P-450 Enzyme System; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases