Thalassemia and malaria: New insights into an old problem
Thalassemia and malaria: New insights into an old problem
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DOI：
10.1046/j.1525-1381.1999.99235.x
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发表时间：
1999-07-01
期刊：
影响因子：
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通讯作者：
Weatherall, DJ
中科院分区：
文献类型：
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作者：
Clegg, JB;Weatherall, DJ
血红蛋白病可能是世界上最常见的遗传性疾病：世界卫生组织估计，至少有5%的人口是一种或另一种最严重的形式，α-和β-地中海贫血和结构变异血红蛋白S，C和E的携带者，在许多国家发现多态性频率。所有这些血红蛋白病都被认为可以保护人们免受疟疾的侵害，人们认为，在世界上疟疾肆虐的地区，自然选择是提高和维持其基因频率的原因，这一想法是50年前由J.B.S. 1950年代在非洲对血红蛋白S进行的流行病学研究为“疟疾假说”提供了支持，但直到最近，证明地中海贫血症的流行病学研究极为困难。然而，分子方法的应用为解决这个老问题提供了新的机会。对地中海贫血变异体进行的人口和分子遗传分析，以及对西南太平洋α地中海贫血与疟疾之间关系进行的微流行病学研究，为保护提供了明确的证据。令人惊讶的是，这种保护似乎来自非常年轻的地中海贫血儿童对恶性疟原虫，特别是间日疟原虫的易感性增强，这种早期暴露似乎为以后的生活提供了更好的保护。
The hemoglobinopathies are probably the world's most common genetic diseases: The World Health Organization has estimated that at least 5% of the population are carriers for one or other of the most serious forms, the alpha- and beta-thalassemias and the structural variant hemoglobins S, C, and E, which an found at polymorphic frequencies in many countries. All these hemoglobinopathies are believed to provide protection against malaria, and it is thought that, in malarial regions of the world, natural selection has been responsible for elevating and maintaining their gene frequencies, an idea first proposed 50 years ago by J.B.S. Haldane.Epidemiological studies undertaken in the 1950s on hemoglobin S in Africa provided support for the "malaria hypothesis," but until recently it has proved extremely difficult to verify it for the thalassemias. The application of molecular methods has, however, provided new opportunities to address this old question. Population and molecular genetic analysis of thalassemia variants, and microepidemiological studies of the relationship between alpha-thalassemia and malaria in the southwest Pacific, have provided unequivocal evidence for protection. Surprisingly, some of this protection appears to derive from enhanced susceptibility in very young thalassemic children to both Plasmodium falciparum and, especially, P. vivax, and this early exposure appears to provide the basis for better protection in later life.