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
Volume34
Issue3
Pagination523-32
Date Published2002 Aug
ISSN0360-2532
KeywordsAnimals, Base Sequence, Ethnic Groups, Genotype, Humans, Isoenzymes, Methylamines, Molecular Sequence Data, Multigene Family, Oxygenases, Polymorphism, Genetic, Xenobiotics
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.

DOI10.1081/DMR-120005653
Alternate JournalDrug Metab. Rev.
PubMed ID12214664
Grant ListR01 HL038650 / HL / NHLBI NIH HHS / United States
HL38650 / HL / NHLBI NIH HHS / United States