Shimizu Makiko, Cashman John R, Yamazaki Hiroshi
Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan.
BMC Med Genet. 2007 Jan 27;8:2. doi: 10.1186/1471-2350-8-2.
Trimethylaminuria, or fish odor syndrome, includes a transient or mild malodor caused by an excessive amount of malodorous trimethylamine as a result of body secretions. Herein, we describe data to support the proposal that menses can be an additional factor causing transient trimethylaminuria in self-reported subjects suffering from malodor and even in healthy women harboring functionally active flavin-containing monooxygenase 3 (FMO3).
FMO3 metabolic capacity (conversion of trimethylamine to trimethylamine N-oxide) was defined as the urinary ratio of trimethylamine N-oxide to total trimethylamine.
Self-reported Case (A) that was homozygous for inactive Arg500stop FMO3, showed decreased metabolic capacity of FMO3 (i.e., approximately 10% the unaffected metabolic capacity) during 120 days of observation. For Case (B) that was homozygous for common [Glu158Lys; Glu308Gly] FMO3 polymorphisms, metabolic capacity of FMO3 was almost approximately 90%, except for a few days surrounding menstruation showing < 40% metabolic capacity. In comparison, three healthy control subjects that harbored heterozygous polymorphisms for [Glu158Lys; Glu308Gly] FMO3 or homozygous for wild FMO3 showed normal (> 90%) metabolic capacity, however, on days around menstruation the FMO3 metabolic capacity was decreased to ~60-70%.
Together, these results indicate that abnormal FMO3 capacity is caused by menstruation particularly in the presence, in homozygous form, of mild genetic variants such as [Glu158Lys; Glu308Gly] that cause a reduced FMO3 function.
三甲胺尿症,即鱼腥味综合征,是由于身体分泌物中产生过量有恶臭的三甲胺而导致的一种短暂或轻微的恶臭。在此,我们描述相关数据以支持如下观点:月经可能是导致自我报告有恶臭的受试者出现短暂性三甲胺尿症的一个额外因素,甚至对于携带功能活跃的含黄素单加氧酶3(FMO3)的健康女性也是如此。
FMO3的代谢能力(三甲胺转化为三甲胺N-氧化物)定义为尿中三甲胺N-氧化物与总三甲胺的比值。
自我报告的病例(A)为无活性的Arg500stop FMO3纯合子,在120天的观察期内,其FMO3代谢能力下降(即约为未受影响代谢能力的10%)。对于常见的[Glu158Lys;Glu308Gly] FMO3多态性纯合子的病例(B),除月经前后几天代谢能力<40%外,FMO3的代谢能力几乎约为90%。相比之下,三名携带[Glu158Lys;Glu308Gly] FMO3杂合多态性或野生FMO3纯合子的健康对照受试者显示出正常(>90%)的代谢能力,然而,在月经前后几天,FMO3代谢能力降至约60 - 70%。
总之,这些结果表明,月经会导致FMO3能力异常,特别是在存在如[Glu158Lys;Glu308Gly]这种导致FMO3功能降低的轻度基因变异的纯合形式时。