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关于斯巴丁在恩加韦·瓜伊米美洲印第安人中的瞬时多态性氧化的初步说明:一个具有该途径暂定系统发育时间框架的遗传分化案例。

A preliminary note on the transient polymorphic oxidation of sparteine in the Ngawbé Guaymí Amerindians: a case of genetic divergence with tentative phylogenetic time frame for the pathway.

作者信息

Arias T D, Inaba T, Cooke R G, Jorge L F

机构信息

World Health Organization Collaborating Center for Drug Quality Control, University of Panama, República de Panamá.

出版信息

Clin Pharmacol Ther. 1988 Sep;44(3):343-52. doi: 10.1038/clpt.1988.160.

Abstract

The oxidation of sparteine was studied in a total of 121 Ngawbé Guaymí volunteers in Panama, 97 of whom were unrelated. When presented in a frequency histogram, the results of the log10 of the metabolic ratios (LMR) indicated the existence of two modes, the largest of which exhibited a normal distribution (alpha = 0.05; chi 2 = 5.46). A preliminary assignment of an antimode for this population sample is proposed, located within the region of LMR 0.65 to 0.85 vs LMR of 1.3 for white subjects, and results in five poor metabolizers (PMs) (5.2%). This is in contrast to the absence of PMs (0/210) we have reported for the Cuna Amerindians. The microevolution of the sparteine route, corresponding to a tenfold change in the frequency of PMs, is likely to have occurred within their genetic divergence time. These observations of the divergence of a metabolic route of therapeutic importance and the proposal of a time frame for its microevolution constitute the first cases in the literature.

摘要

在巴拿马的121名恩加韦·瓜伊米志愿者中研究了司巴丁的氧化情况,其中97人无亲缘关系。当以频率直方图呈现时,代谢比(LMR)的log10结果显示存在两种模式,其中最大的一种呈现正态分布(α = 0.05;χ2 = 5.46)。针对该人群样本初步提出了一个反众数,位于LMR为0.65至0.85的区域,而白种人的LMR为1.3,该人群中有5名慢代谢者(PMs)(5.2%)。这与我们报道的库纳美洲印第安人无慢代谢者(0/210)的情况形成对比。司巴丁代谢途径的微进化,对应着慢代谢者频率的十倍变化,很可能发生在他们的遗传分化时期内。这些关于具有治疗重要性的代谢途径差异的观察结果以及其微进化时间框架的提议,构成了文献中的首例。

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