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Natural selection of hemi- and heterozygotes for G6PD deficiency in Africa by resistance to severe malaria.

机译：通过对严重疟疾的抗性自然选择非洲的G6PD缺陷的半合子和杂合子。

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摘要

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common enzymopathy of humans, affects over 400 million people. The geographical correlation of its distribution with the historical endemicity of malaria suggests that this disorder has risen in frequency through natural selection by malaria. However, attempts to confirm that G6PD deficiency is protective in case-control studies of malaria have yielded conflicting results. Hence, for this X-linked disorder, it is unclear whether both male hemizygotes and female heterozygotes are protected or, as frequently suggested, only females. Furthermore, how much protection may be afforded is unknown. Here we report that, in two large case-control studies of over 2,000 African children, the common African form of G6PD deficiency (G6PD A-) is associated with a 46-58% reduction in risk of severe malaria for both female heterozygotes and male hemizygotes. A mathematical model incorporating the measured selective advantage against malaria suggests that a counterbalancing selective disadvantage, associated with this enzyme deficiency, has retarded its rise in frequency in malaria-endemic regions. Although G6PD deficiency is now regarded as a generally benign disorder, in earlier environmental conditions it could have been significantly disadvantageous.
机译：6-磷酸葡萄糖脱氢酶（G6PD）缺乏症是人类最常见的酶病，影响了超过4亿人。其分布与疟疾的历史流行性的地理相关性表明，这种疾病的发生频率是通过疟疾的自然选择而增加的。但是，试图确认G6PD缺乏症在疟疾的病例对照研究中具有保护作用，但结果却相矛盾。因此，对于这种与X连锁的疾病，目前尚不清楚男性半合子和女性杂合子是否都受到保护，或者经常建议仅女性受到保护。此外，尚不清楚可以提供多少保护。在这里，我们报告说，在两项针对2,000多名非洲儿童的大型病例对照研究中，非洲常见的G6PD缺乏症（G6PD A-）与女性杂合子和男性患严重疟疾的风险降低46-58％有关半合子。结合所测得的针对疟疾的选择性优势的数学模型表明，与这种酶缺乏症相关的平衡选择性劣势已经阻碍了其在疟疾流行地区的频率上升。尽管现在已将G6PD缺乏症视为一种普遍的良性疾病，但在较早的环境条件下，它可能一直处于不利地位。

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