期刊
PHARMACOLOGY & THERAPEUTICS
卷 106, 期 1, 页码 19-38出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pharmthera.2004.11.001
关键词
cis-regulatory; polymorphism; pharmacogenetics; pharmacogenomics; SNP; RNA; allele-specific; genotype-phenotype; cytochrome; review
资金
- NIDA NIH HHS [DA018744] Funding Source: Medline
Functional polymorphisms that alter gene expression and mRNA processing appear to play a critical role in shaping human phenotypic variability. Intensive studies on polymorphisms affecting drug response have revealed multiple modes of altered gene function, frequently involving cis-acting regulatory sequence variants. Experimental and in silico methods have advanced the search for such polymorphisms, but considerable challenges remain. Here, a survey of polymorphisms in drug-related genes indicates that: (a) a substantial proportion of genetic variability still remains unaccounted for; (b) a majority of these genes harbors known regulatory polymorphisms; and (c) a portion of polymorphisms affect splicing and mRNA turnover. Pharmacogenetic optimiziation of individual drug therapy may require a complete understanding of all functional sequence variants in key genes. This review surveys known noncoding polymorphisms in genes encoding cytochrome P450s and other drug-metabolizing enzymes, drug transporters, and drug targets and receptors. Current methods and challenges associated with the identification and characterization of functional polyrnorphisms are also discussed. (c) 2004 Elsevier Inc. All rights reserved.
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