Seasonal childhood anaemia in West Africa is associated with the haptoglobin 2-2 genotype.
Seasonal childhood anaemia in West Africa is associated with the haptoglobin 2-2 genotype.
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DOI：
10.1371/journal.pmed.0030172
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发表时间：
2006-05
期刊：
影响因子：
15.8
通讯作者：
Prentice, Andrew M.
中科院分区：
文献类型：
--
作者：
Atkinson, Sarah H.;Rockett, Kirk;Sirugo, Giorgio;Bejon, Philip A.;Fulford, Anthony;O'Connell, Maria A.;Bailey, Robin;Kwiatkowski, Dominic P.;Prentice, Andrew M.
贫血是非洲儿童发病和死亡的主要原因。血浆蛋白结合珠蛋白（Hp）与疟疾引起的溶血后释放的游离血红蛋白结合。结合珠蛋白多态性导致蛋白质具有改变的血红蛋白结合能力和不同的抗氧化剂、铁循环和免疫功能。以往的研究探讨了触珠蛋白多态性在疟疾和铁稳态中的重要性，但尚不清楚触珠蛋白基因型是否可能是疟疾流行区儿童贫血的危险因素。在疟疾季节开始和结束时，对780名2-6岁的冈比亚农村儿童进行了调查。采集样本以评估血红蛋白（Hb）浓度、铁状态（铁蛋白、锌原卟啉、转铁蛋白饱和度和可溶性转铁蛋白受体浓度）、触珠蛋白浓度、α-1-抗胰凝乳蛋白酶（炎症指标）和血膜上的疟疾寄生虫。我们提取DNA并对结合珠蛋白、镰状细胞和葡萄糖-6-磷酸（G6 PD）缺乏症进行基因分型。平均血红蛋白水平在疟疾季节下降。与其他儿童（下降5.1 g/l; CI 3.8，6.4）相比，具有触珠蛋白2-2基因型的儿童（17%）在疟疾季节的Hb水平平均下降更大（下降8.9 g/l; CI 5.7，12.1）。在多变量回归分析中，控制基线Hb水平、年龄组、村庄、血膜上的疟原虫、铁状态、触珠蛋白浓度和G6 PD缺乏，触珠蛋白基因型预测了疟疾季节结束时的Hb水平（p = 0.0009，系数=-4.2）。结合珠蛋白基因型不影响铁的状态。 在疟疾流行区，触珠蛋白2-2基因型是儿童贫血的危险因素，这一发现可能反映了在疟疾诱导的溶血后，Hp 2 -2聚合物抑制游离血红蛋白-铁的能力降低。触珠蛋白基因型的影响程度（4 g/l Hb差异，p = 0.0009）与G6 PD缺乏或HbAS的影响程度相当（分别为3 g/l差异，p = 0.03;和2 g/l差异，p = 0.68）。 结合珠蛋白2-2基因型似乎是疟疾流行区儿童贫血的一个危险因素，可能反映了在疟疾诱导的溶血后，Hp 2 -2聚合物抑制游离血红蛋白-铁的能力降低。
Anaemia is a major cause of morbidity and mortality for children in Africa. The plasma protein haptoglobin (Hp) binds avidly to free haemoglobin released following malaria-induced haemolysis. Haptoglobin polymorphisms result in proteins with altered haemoglobin-binding capacity and different antioxidant, iron-recycling, and immune functions. Previous studies examined the importance of haptoglobin polymorphism in malaria and iron homeostasis, but it is unknown whether haptoglobin genotype might be a risk factor for anaemia in children in a malaria-endemic area. A cohort of 780 rural Gambian children aged 2–6 y was surveyed at the start and end of the malaria season. Samples were taken to assess haemoglobin (Hb) concentration, iron status (ferritin, zinc protoporphyrin, transferrin saturation, and soluble transferrin receptor concentration), haptoglobin concentration, α-1-antichymotrypsin (a measure of inflammation), and malaria parasites on blood film. We extracted DNA and genotyped for haptoglobin, sickle cell, and glucose-6-phosphate (G6PD) deficiency. Mean Hb levels fell over the malaria season. Children with the haptoglobin 2-2 genotype (17%) had a greater mean drop in Hb level over the malaria season (an 8.9 g/l drop; confidence interval [CI] 5.7, 12.1) compared to other children (a 5.1 g/l drop; CI 3.8, 6.4). In multivariate regression analysis, controlling for baseline Hb level, age group, village, malaria parasites on blood film, iron status, haptoglobin concentration, and G6PD deficiency, haptoglobin genotype predicted Hb level at the end of the malaria season ( p = 0.0009, coefficient = −4.2). Iron status was not influenced by haptoglobin genotype. The finding that haptoglobin 2-2 genotype is a risk factor for anaemia in children in a malaria-endemic area may reflect the reduced ability of the Hp2-2 polymer to scavenge free haemoglobin-iron following malaria-induced haemolysis. The magnitude of the effect of haptoglobin genotype (4 g/l Hb difference, p = 0.0009) was comparable to that of G6PD deficiency or HbAS (3 g/l difference, p = 0.03; and 2 g/l difference, p = 0.68, respectively). Haptoglobin 2-2 genotype seems to be a risk factor for anaemia in children in a malaria-endemic area, possibly reflecting the reduced ability of the Hp2-2 polymer to scavenge free haemoglobin-iron following malaria-induced haemolysis.
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6.5
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