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Research ArticleArticle

Identification of Novel Variants of the Flavin-Containing Monooxygenase Gene Family in African Americans

Bjarte Furnes, Jinong Feng, Steve S. Sommer and Daniel Schlenk
Drug Metabolism and Disposition February 2003, 31 (2) 187-193; DOI: https://doi.org/10.1124/dmd.31.2.187
Bjarte Furnes
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Jinong Feng
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Steve S. Sommer
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Daniel Schlenk
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Abstract

Sequence polymorphisms in enzymes involved in drug metabolism have been widely implicated in the differences observed in the sensitivity to various xenobiotics. The flavin-containing monooxygenase (FMO) gene family in humans catalyzes the monooxygenation of numerous N-, P- and S-containing drugs, pesticides, and environmental toxicants. Six genes (FMO1–6) have been identified so far, but the major alleles of FMO2 and FMO6 encode nonfunctional proteins due to a nonsense mutation and splice-site abnormalities, respectively. Data on structural variants exist for humanFMO2 and 3, whereas very little is known about the other FMO genes. FMO1–6 were scanned in 50 individuals of African-American descent using the method, detection of virtually all mutations-single-strand conformational polymorphism. A total of 49 sequence variants were identified in a total 1.35 megabases of scanned sequence, of which 29 were variants affecting protein structure or expression. Some of these are expected to affect the activity of the protein, including a nonsense mutation in FMO1 (R502X) and missense mutations in FMO1 (I303T), FMO4 (E339Q), and FMO5 (P457L) that occur in highly conserved amino acids. Additional deleterious substitutions in FMO2 (del337G) and FMO6 (Q105X) were also identified. Multiple structural variants in the FMO gene family were observed in this African-American sample. Some of the substitutions identified in this study might be useful markers in future association studies assessing sensitivity to environmental toxicants and common disease.

Footnotes

  • Abbreviations used are::
    FMO
    flavin-containing monooxygenase
    P450
    cytochrome P450
    SNP
    single nucleotide polymorphism
    DOVAM-S
    detection of virtually all mutations-single-strand conformational polymorphism
    PCR
    polymerase chain reaction
    PAGE
    polyacrylamide gel electrophoresis
    VAPSE
    variants affecting protein structure or expression
    TBE
    Tris borate-EDTA
    CAPSO
    3-(cyclohexylamino)-2-hydroxy-1-propanesulfonic acid
    a.a.
    amino acids
    • Received August 20, 2002.
    • Accepted November 5, 2002.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 31 (2)
Drug Metabolism and Disposition
Vol. 31, Issue 2
1 Feb 2003
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Research ArticleArticle

Identification of Novel Variants of the Flavin-Containing Monooxygenase Gene Family in African Americans

Bjarte Furnes, Jinong Feng, Steve S. Sommer and Daniel Schlenk
Drug Metabolism and Disposition February 1, 2003, 31 (2) 187-193; DOI: https://doi.org/10.1124/dmd.31.2.187

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Research ArticleArticle

Identification of Novel Variants of the Flavin-Containing Monooxygenase Gene Family in African Americans

Bjarte Furnes, Jinong Feng, Steve S. Sommer and Daniel Schlenk
Drug Metabolism and Disposition February 1, 2003, 31 (2) 187-193; DOI: https://doi.org/10.1124/dmd.31.2.187
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