[Future direction of pharmacogenomics: identification of genes associated with risk of adverse drug reactions using genome-wide association study].
Drug-induced skin rash characterized by an acute inflammatory reaction of skin and mucous membranes is dose-independent, unpredictable, and sometimes life-threatening. In recent years, the U.S. Food and Drug Administration (FDA) has recommended genotyping of polymorphisms in the human leukocyte antigen (HLA) prior to drug administration for the avoidance of severe skin rash induced by drugs, such as abacavir and carbamazepine. A genome-wide association study (GWAS) is useful for the identification of genomic biomarkers that can predict the efficacy or risk of toxicity of various drugs. We identified novel susceptibility loci associated with the risk of a skin rash induced by nevirapine and carbamazepine in Thai and Japanese populations, respectively, through case-control GWAS with high-throughput single-nucleotide polymorphism (SNP) genotyping technology. In order to apply the genomic biomarkers to clinical therapeutics, prospective clinical trials will be necessary for the evaluation of an intervention based on genetic tests.
Taisei
T
Mushiroda
D000927:Anticonvulsants / Q000009:adverse effects; D002220:Carbamazepine / Q000009:adverse effects; D015224:Dideoxynucleosides / Q000008:administration & dosage; D003875:Drug Eruptions / Q000209:etiology* / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D060005:Genotyping Techniques; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D019829:Nevirapine / Q000009:adverse effects; D010597:Pharmacogenetics / Q000639:trends*; D011110:Polymorphism, Genetic / Q000235:genetics; D012306:Risk; D000099227:Abacavir
D000927:Anticonvulsants; D002220:Carbamazepine; D015224:Dideoxynucleosides; D006680:HLA Antigens; D047908:Intracellular Signaling Peptides and Proteins; D019829:Nevirapine; D000099227:Abacavir; C412616:CCHCR1 protein, human