Ethnic differences in human flavin-containing monooxygenase 2 (FMO2) polymorphisms: Detection of expressed protein in African-America

The flavin-containing monooxygenases (FMOs) are a family of xenobiotic-meta bolizing enzymes that are expressed in a species- and tissue-specific manne r. FMO2 expression has been observed in pulmonary tissue from several speci es, but not human. Two human FMO2 point mutations have been reported: a cyt osine to thymidine transition at position 1414 resulting in a premature sto p codon and a thymidine insertion at position 1589 resulting in a frameshif t. To define the frequency of these sequence variations and explore their s ignificance, unrelated African-American, Caucasian, and Korean individuals were genotyped. In the African-American population tested (n = 180), the 14 14C allele occurred at a 13% frequency; however, all of the tested Caucasia ns (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 activi ty. Western blot analysis of pulmonary microsomes failed to detect immunore active 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 w ith the 1414C allele encoding an active FMO2 enzyme. FMO2 mRNA expression w as observed in most individuals, but failed to correlate with genotype or p rotein expression. In summary, functional FMO2 is expressed in only a small percentage of the overall population. However, in certain ethnic groups, a ctive pulmonary FMO2 enzyme will be present in a significant number of indi viduals. (C) 2000 Academic Press.