Haemoglobin C protects against clinical Plasmodium falciparum malaria
Haemoglobin C protects against clinical Plasmodium falciparum malaria
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DOI：
10.1038/35104556
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发表时间：
2001-11-15
期刊：
影响因子：
64.8
通讯作者：
Coluzzi, M
中科院分区：
文献类型：
--
作者：
Modiano, D;Luoni, G;Coluzzi, M
血红蛋白C（HbC; β 6 Glu--> Lys）常见于西非疟疾流行地区，尤其是布基纳法索（1，2）。关于血红蛋白S（HbS; β 6 Glu-->瓦尔）杂合性对严重疟疾的保护作用存在结论性证据（3），而关于HbC性状的矛盾结果已被报道（4-10），并且关于HbCC基因型的可能作用不存在流行病学数据。体外研究表明，HbCC红细胞不能支持恶性疟原虫的生长（11，12），但已观察到具有高恶性疟原虫寄生虫血症的HbC纯合子（10）。在布基纳法索对4，348名Mossi受试者进行的一项大型病例对照研究中，HbC与HbAC杂合子中临床疟疾风险降低29%（P = 0.0008）和HbCC纯合子中临床疟疾风险降低93%（P = 0.0011）相关。这些发现，以及与严重不利的HbSS和HbSC基因型相比，HbAC和HbCC（13）的病理学有限，以及β（C1，2，14）地理中心的低β（S）基因频率，支持以下假设：从长远来看，在没有疟疾控制的情况下，HbC将在西非中部取代HbS。
Haemoglobin C (HbC; beta 6Glu --> Lys) is common in malarious areas of West Africa, especially in Burkina Faso(1,2). Conclusive evidence exists on the protective role against severe malaria of haemoglobin S (HbS; beta 6Glu --> Val) heterozygosity(3), whereas conflicting results for the HbC trait have been reported(4-10) and no epidemiological data exist on the possible role of the HbCC genotype. In vitro studies suggested that HbCC erythrocytes fail to support the growth of P. falciparum(11,12) but HbC homozygotes with high P. falciparum parasitaemias have been observed(10). Here we show, in a large case-control study performed in Burkina Faso on 4,348 Mossi subjects, that HbC is associated with a 29% reduction in risk of clinical malaria in HbAC heterozygotes (P = 0.0008) and of 93% in HbCC homozygotes (P = 0.0011). These findings, together with the limited pathology of HbAC and HbCC(13) compared to the severely disadvantaged HbSS and HbSC genotypes and the low beta (S) gene frequency in the geographic epicentre of beta (C1,2,14), support the hypothesis that, in the long term and in the absence of malaria control, HbC would replace HbS in central West Africa.