Ethnic Differences in Human Flavin-Containing Monooxygenase 2 (FMO2) Polymorphisms: Detection of Expressed Protein in African-Americans

The flavin-containing monooxygenases (FMOs) are a family of xenobiotic-metabolizing enzymes that are expressed in a species- and tissue-specific manner. FMO2 expression has been observed in pulmonary tissue from several species, but not human. Two human FMO2 point mutations have been reported: a cyt...

Full description

Saved in:

Bibliographic Details
Published in:	Toxicology and applied pharmacology Vol. 168; no. 3; pp. 216 - 224
Main Authors:	Whetstine, J.R, Yueh, M.-F, Hopp, K.A, McCarver, D.G, Williams, D.E, Park, C.-S, Kang, J.H, Cha, Y.-N, Dolphin, C.T, Shephard, E.A, Phillips, I.R, Hines, R.N
Format:	Journal Article
Language:	English
Published:	San Diego, CA Elsevier Inc 01-11-2000 Elsevier
Subjects:	African Americans Alleles Analytical, structural and metabolic biochemistry Biological and medical sciences Black or African American Black People - genetics Blotting, Western Enzymes and enzyme inhibitors ethnic differences flavin-containing monooxygenase FMO2 Fundamental and applied biological sciences. Psychology Genotype human Humans Oligonucleotides - analysis Oligonucleotides - genetics Oxygenases - biosynthesis Oxygenases - genetics polymorphism Polymorphism, Genetic - genetics Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - biosynthesis RNA, Messenger - genetics Transferases United States United States flavin-containing monooxygenase FMO2 polymorphism human ethnic differences Human Flavin enzyme Ethnic origin American Enzyme Gene product Lung Genetic variant Genotype Gene expression Respiratory system In vitro African Heterozygosity Dimethylaniline monooxygenase (N-oxide-forming) Tissue Allele DNA Drug-metabolizing enzyme Genetics Oxidoreductases Mutation Genome Polymorphism
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	The flavin-containing monooxygenases (FMOs) are a family of xenobiotic-metabolizing enzymes that are expressed in a species- and tissue-specific manner. FMO2 expression has been observed in pulmonary tissue from several species, but not human. Two human FMO2 point mutations have been reported: a cytosine to thymidine transition at position 1414 resulting in a premature stop codon and a thymidine insertion at position 1589 resulting in a frameshift. To define the frequency of these sequence variations and explore their significance, unrelated African-American, Caucasian, and Korean individuals were genotyped. In the African-American population tested (n = 180), the 1414C allele occurred at a 13% frequency; however, all of the tested Caucasians (n = 52) and Koreans (n = 100) were homozygous for the 1414T allele. The T1589 allele occurred at frequencies of 6.9 and 13.0% in African-Americans (n = 175) and Caucasians (n = 23), respectively, and appears to segregate with the 1414T allele. Thus, it would have no further impact on FMO2 activity. Western blot analysis of pulmonary microsomes failed to detect immunoreactive protein in 1414T homozygotes. A heterozygotic individual did exhibit a single band of the expected size, but no detectable FMO activity in the corresponding lung microsomes. Sequence analysis, however, was consistent with the 1414C allele encoding an active FMO2 enzyme. FMO2 mRNA expression was observed in most individuals, but failed to correlate with genotype or protein expression. In summary, functional FMO2 is expressed in only a small percentage of the overall population. However, in certain ethnic groups, active pulmonary FMO2 enzyme will be present in a significant number of individuals.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0041-008X 1096-0333
DOI:	10.1006/taap.2000.9050