TitleGenetic polymorphisms of flavin-containing monooxygenase (FMO).
Publication TypeJournal Article
Year of Publication2002
AuthorsKrueger SK, Williams DE, Yueh M-F, Martin SR, Hines RN, Raucy JL, Dolphin CT, Shephard EA, Phillips IR
JournalDrug Metab Rev
Date Published2002 Aug
KeywordsAnimals, Base Sequence, Ethnic Groups, Genotype, Humans, Isoenzymes, Methylamines, Molecular Sequence Data, Multigene Family, Oxygenases, Polymorphism, Genetic, Xenobiotics

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.

Alternate JournalDrug Metab. Rev.
PubMed ID12214664
Grant ListR01 HL038650 / HL / NHLBI NIH HHS / United States
HL38650 / HL / NHLBI NIH HHS / United States