Ethnic differences in human flavin-containing monooxygenase 2 (FMO2) polymorphisms: detection of expressed protein in African-Americans.
Ethnic differences in human flavin-containing monooxygenase 2 (FMO2) polymorphisms: detection of expressed protein in African-Americans.
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DOI：
10.1006/taap.2000.9050
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发表时间：
2000-11
影响因子：
3.8
通讯作者：
J. Whetstine;M. Yueh;K. Hopp;D. McCarver;D. Williams;C-S Park;J. Kang;Y. Cha;C. Dolphin;E. Shephard;I. Phillips;R. Hines
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文献类型：
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作者：
J. Whetstine;M. Yueh;K. Hopp;D. McCarver;D. Williams;C-S Park;J. Kang;Y. Cha;C. Dolphin;E. Shephard;I. Phillips;R. Hines
含有黄素的单加氧酶(FMOS)是一个异源代谢酶家族，以物种和组织特异性的方式表达。FMO2在几个物种的肺组织中都有表达，但在人类中没有。已经报道了人类FMO2的两个点突变：1414位胞嘧啶到胸腺嘧啶核苷的转变导致提前终止密码子和1589位胸苷插入导致移码。为了确定这些序列变异的频率并探索它们的意义，对无关的非裔美国人、高加索人和韩国人进行了基因分型。在被测试的非裔美国人中(n=180)，1414C等位基因的出现频率为13%；然而，所有被测试的高加索人(n=52)和韩国人(n=100)的1414T等位基因都是纯合的。T1589等位基因在非洲裔美国人(n=175)和高加索人(n=23)中的频率分别为6.9%和13.0%，并与1414T等位基因分离。因此，它不会对FMO2活性产生进一步的影响。1414T纯合子肺微粒体的免疫印迹分析未能检测到免疫反应蛋白。杂合子个体确实表现出预期大小的单一条带，但在相应的肺微粒体中没有检测到FMO活性。然而，序列分析与编码活性FMO2酶的1414C等位基因一致。FMO2mRNA在大多数个体中都有表达，但与基因或蛋白表达无关。总而言之，功能性FMO2仅在总人口中的一小部分表达。然而，在某些民族中，肺FMO2酶活性将存在于相当数量的个体中。
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.