Genetic polymorphisms of flavin-containing monooxygenase (FMO)

Drug Metab Rev. 2002 Aug;34(3):523-32. doi: 10.1081/dmr-120005653.

Abstract

Mammalian flavin-containing monooxygenase (FMO) exists as six gene families and metabolizes a plethora of drugs and xenobiotics. The major FMO in adult human liver, FMO3, is responsible for trimethylamine (TMA) N-oxygenation. A number of FMO3 mutant alleles have been described and associated with a disease termed trimethylaminuria (TMAU). The TMAU patient excretes large amounts of TMA in urine and sweat. A more recent ethnically related polymorphism in expression of the major FMO in lung, FMO2, has been described. All Caucasians and Asians genotyped to date are homozygous for a CAG --> TAG amber mutation resulting in a premature stop codon and a nonfunctional protein truncated at AA 472 (wildtype FMO2 is 535 AA). This allele has been designated hFMO2*2A. Twenty-six percent of individuals of African descent and 5% of Hispanics genotyped to date carry at least one allele coding for full-length FMO2 (hFMO2*1 allele). Preliminary evidence indicates that FMO2.1 is very active toward the S-oxygenation of low MW thioureas, including the lung toxicant ethylene thiourea. Polymorphic expression of functional FMO2 in the individuals of African and Hispanic descent may markedly influence drug metabolism and/or xenobiotic toxicity in the lung.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Base Sequence
  • Ethnic Groups / genetics
  • Genotype
  • Humans
  • Isoenzymes / genetics*
  • Methylamines / metabolism
  • Molecular Sequence Data
  • Multigene Family
  • Oxygenases / genetics*
  • Polymorphism, Genetic*
  • Xenobiotics / metabolism

Substances

  • Isoenzymes
  • Methylamines
  • Xenobiotics
  • Oxygenases
  • dimethylaniline monooxygenase (N-oxide forming)
  • trimethylamine