title: Allopurinol pharmacogenetics: assessment of potential clinical usefulness.
abstract: Use of pharmacogenetics to inform treatment decisions remains a priority for clinicians, patients and public health agencies. We previously developed a framework for systematically assessing whether pharmacogenetic test information would likely bring value to clinical decision-making and enjoy practical uptake. We applied this tool to allopurinol to determine potential usefulness of HLA genetic information in assessing risk for allopurinol-induced severe cutaneous adverse reactions. We quantified allopurinol use data and the magnitude of adverse event signals using US FDA databases, reviewed reported cases of allopurinol-associated severe cutaneous adverse reactions to assess whether clinical subtypes of patients could be identified, performed pooled analyses of associations between HLA variation and allopurinol-induced severe cutaneous adverse reactions and described considerations in clinical implementation of allopurinol pharmacogenetics.
authors: Genomics Group, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation & Research, US FDA, Silver Spring, MD 20993, USA. issam.zineh@fda.hhs.gov
authors: Issam
authors: I
authors: Zineh
authors: Padmaja
authors: P
authors: Mummaneni
authors: Jenna
authors: J
authors: Lyndly
authors: Shashi
authors: S
authors: Amur
authors: Lois A
authors: LA
authors: La Grenade
authors: Stephen H
authors: SH
authors: Chang
authors: Hobart
authors: H
authors: Rogers
authors: Michael A
authors: MA
authors: Pacanowski
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000493:Allopurinol / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D004892:Erythema Multiforme / Q000139:chemically induced / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D005820:Genetic Testing / Q000379:methods*; D014644:Genetic Variation; D006073:Gout / Q000188:drug therapy; D006074:Gout Suppressants / Q000009:adverse effects* / Q000627:therapeutic use; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D033461:Hyperuricemia / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D018570:Risk Assessment; D012871:Skin Diseases / Q000139:chemically induced / Q000235:genetics*; D013262:Stevens-Johnson Syndrome / Q000139:chemically induced / Q000209:etiology / Q000235:genetics
chemical_list: D006074:Gout Suppressants; D006680:HLA Antigens; D000493:Allopurinol