The Flavin-Containing Monoooxygenases (FMOs): Genetic Variation and its Consequences for the Metabolism of Therapeutic Drugs

Author(s): Ian R. Phillips, Asvi A. Francois, Elizabeth A. Shephard

Journal Name: Current Pharmacogenomics
Continued as Current Pharmacogenomics and Personalized Medicine

Volume 5 , Issue 4 , 2007

Abstract:

Flavin-containing monoooxygenases (FMOs) are a family of enzymes involved in the metabolism of foreign chemicals, including many therapeutic drugs. In this review we focus on the functional FMOs of humans (FMOs 1, 2, 3, 4 and 5). For each FMO we describe its gene organization, developmental- and tissue-specific pattern of expression, substrate specificity and the identity, frequency and functional effect of polymorphic variants. We also review the consequences of genetic variation in the FMOs for the metabolism of therapeutic drugs and the implications of this for drug efficacy and response. Some key points are: the majority of humans are homozygous for an allele (FMO2ast;2) that encodes a truncated, non-functional polypeptide, but a substantial proportion of individuals of African descent possess a copy of the functional ancestral (FMO2*1) allele and thus are predicted to respond differently to drugs and other foreign chemicals that are substrates for FMO2; FMO3 polymorphisms that decrease catalytic activity have been linked to increased drug efficacy; rare mutations in FMO3 are causative of the disorder trimethylaminuria; and the role of FMO1 and FMO3 in the oxidation of the antiestrogen tamoxifen and the antitubercular drug thiacetazone are discussed.

Keywords: human FMO1 gene, cytochrome P450, coding variants, FMO2 expression, Trimethylaminuria

Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 5
ISSUE: 4
Year: 2007
Page: [292 - 313]
Pages: 22
DOI: 10.2174/157016007782793683
Price: $58

Article Metrics

PDF: 4