Institut Pasteur, Laboratoire de la Génétique de la réponse aux infections chez l'homme, 75724 Paris, France.
Science. 2009 Dec 11;326(5959):1546-9. doi: 10.1126/science.1178849.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency--the most common known enzymopathy--is associated with neonatal jaundice and hemolytic anemia usually after exposure to certain infections, foods, or medications. Although G6PD-deficient alleles appear to confer a protective effect against malaria, the link with clinical protection from Plasmodium infection remains unclear. We investigated the effect of a common G6PD deficiency variant in Southeast Asia--the G6PD-Mahidol(487A) variant--on human survival related to vivax and falciparum malaria. Our results show that strong and recent positive selection has targeted the Mahidol variant over the past 1500 years. We found that the G6PD-Mahidol(487A) variant reduces vivax, but not falciparum, parasite density in humans, which indicates that Plasmodium vivax has been a driving force behind the strong selective advantage conferred by this mutation.
葡萄糖-6-磷酸脱氢酶（G6PD）缺乏症——最常见的已知酶病——与新生儿黄疸和溶血性贫血有关，通常在接触某些感染、食物或药物后发生。尽管 G6PD 缺乏等位基因似乎对疟疾具有保护作用，但与 Plasmodium 感染的临床保护之间的联系仍不清楚。我们研究了东南亚常见的 G6PD 缺乏变异——G6PD-Mahidol（487A）变异——对与间日疟和恶性疟有关的人类生存的影响。我们的研究结果表明，在过去的 1500 年中，针对 Mahidol 变异的强烈而近期的正选择已经成为目标。我们发现 G6PD-Mahidol（487A）变异降低了人类间日疟原虫的密度，但不降低恶性疟原虫的密度，这表明间日疟原虫是这种突变赋予的强烈选择优势的驱动力。
