Low plasma haptoglobin is a risk factor for life-threatening childhood severe malarial anemia and not an exclusive consequence of hemolysis.
Low plasma haptoglobin is a risk factor for life-threatening childhood severe malarial anemia and not an exclusive consequence of hemolysis.
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DOI：
10.1038/s41598-018-35944-w
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发表时间：
2018-12-03
影响因子：
4.6
通讯作者：
Fernandez-Reyes D
中科院分区：
文献类型：
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作者：
Abah SE;Burté F;Marquet S;Brown BJ;Akinkunmi F;Oyinloye G;Afolabi NK;Omokhodion S;Lagunju I;Shokunbi WA;Wahlgren M;Dessein H;Argiro L;Dessein AJ;Noyvert B;Hunt L;Elgar G;Sodeinde O;Holder AA;Fernandez-Reyes D
严重疟疾性贫血（SMA）是一种危及生命的儿童恶性疟原虫疟疾综合征，需要紧急输血，表现为炎症和溶血病理。区分溶血引起的低接触红蛋白血症和遗传原因是了解SMA发病机制的关键。我们假设，虽然疟疾引起的低触珠蛋白血症在恢复时应该逆转，但遗传病因不应该逆转。我们在尼日利亚伊巴丹的撒哈拉以南大都市开展了一项病例对照研究，研究对象是生活在高地方性全地方性疟疾负担下的儿童。我们表明，低触珠蛋白血症是儿童SMA的一个危险因素，而不仅仅是由于潜在的分裂性血管内溶血。在表现为SMA的儿童中，低触珠蛋白血症通过恢复期一直持续到恢复，这表明遗传原因。我们发现了一个触珠蛋白基因变异rs12162087 （g.-1203G > a，频率= 0.67）与血浆触珠蛋白水平相关（p = 8.5 × 10−6）。Homo-Var:（AA）与高血浆珠蛋白相关，而参考Homo-Ref:（GG）与低血浆珠蛋白血症相关（p = 2.3 × 10−6）。该变异与SMA相关，最能支持Homo-Ref基因型的风险效应。我们对调节性触珠蛋白基因型和低触珠蛋白血症的见解表明，在无法获得紧急输血的地区，在儿童死亡率高的地区，触珠蛋白筛查可以成为风险评估算法的一部分，以防止疾病迅速发展为SMA。
Severe Malarial Anemia (SMA), a life-threatening childhood Plasmodium falciparum malaria syndrome requiring urgent blood transfusion, exhibits inflammatory and hemolytic pathology. Differentiating between hypo-haptoglobinemia due to hemolysis or that of genetic origin is key to understand SMA pathogenesis. We hypothesized that while malaria-induced hypo-haptoglobinemia should reverse at recovery, that of genetic etiology should not. We carried-out a case-control study of children living under hyper-endemic holoendemic malaria burden in the sub-Saharan metropolis of Ibadan, Nigeria. We show that hypo-haptoglobinemia is a risk factor for childhood SMA and not solely due to intravascular hemolysis from underlying schizogony. In children presenting with SMA, hypo-haptoglobinemia remains through convalescence to recovery suggesting a genetic cause. We identified a haptoglobin gene variant, rs12162087 (g.-1203G > A, frequency = 0.67), to be associated with plasma haptoglobin levels (p = 8.5 × 10−6). The Homo-Var:(AA) is associated with high plasma haptoglobin while the reference Homo-Ref:(GG) is associated with hypo-haptoglobinemia (p = 2.3 × 10−6). The variant is associated with SMA, with the most support for a risk effect for Homo-Ref genotype. Our insights on regulatory haptoglobin genotypes and hypo-haptoglobinemia suggest that haptoglobin screening could be part of risk-assessment algorithms to prevent rapid disease progression towards SMA in regions with no-access to urgent blood transfusion where SMA accounts for high childhood mortality rates.
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