Genetic polymorphisms of flavin-containing monooxygenase (FMO). [Review] [30 refs]

S K Krueger, D E Williams, M F Yueh, S R Martin, R N Hines, J L Raucy, C T Dolphin, E A Shephard, I R Phillips

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)

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. [References: 30]
Original languageEnglish
Pages (from-to)523 - 532
Number of pages10
JournalDrug Metabolism Reviews
Volume34
Issue number3
DOIs
Publication statusPublished - 2002

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