Population genetics of GYPB and association study between GYPB*S/s polymorphism and susceptibility to P. falciparum infection in the Brazilian Amazon.
Population genetics of GYPB and association study between GYPB*S/s polymorphism and susceptibility to P. falciparum infection in the Brazilian Amazon.
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DOI：
10.1371/journal.pone.0016123
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发表时间：
2011-01-24
期刊：
影响因子：
3.7
通讯作者：
Lustigman S
中科院分区：
文献类型：
--
作者：
Tarazona-Santos E;Castilho L;Amaral DR;Costa DC;Furlani NG;Zuccherato LW;Machado M;Reid ME;Zalis MG;Rossit AR;Santos SE;Machado RL;Lustigman S
恶性疟原虫裂殖子利用不同的红细胞受体通过几种途径侵入。田间分离株似乎比实验室分离株使用这些受体的变异性更大。巴西田间分离株显示主要通过血型糖蛋白B（GPB）和/或其他受体利用血型糖蛋白A非依赖性侵袭途径。巴西人群在血型抗原中表现出广泛的多态性，然而，尚未进行研究以将作为恶性疟原虫受体的抗原的流行率与寄生虫的入侵能力联系起来。我们的研究旨在确定GYPB*S/s等位基因的变异是否影响巴西混合人群中恶性疟原虫感染的易感性。研究了来自韦略港的两组巴西亚马逊人：恶性疟原虫感染个体（病例）;和出生和/或在同一流行区生活超过10年的未感染个体（对照），他们暴露于感染，但在研究期间没有患疟疾。用标准方法测定GPB Ss表型和GYPB*S/s等位基因。对每个个体的62个遗传学信息标记进行基因分型，以估计混合物并控制其对GYPB*S频率与疟疾感染之间的关联的潜在影响。 GYPB*S与恶性疟原虫感染的易感性有关，恶性疟原虫感染者GYPB*S/GYPB*S和GYPB*S/GYPB*s的检出率显著高于对照组（69.87% vs.49.75%; P<0.02）。此外，应用于GYPB外显子测序数据的群体遗传学测试表明，自然选择塑造了观察到的核苷酸多样性模式。流行病学和进化方法表明GPB受体在巴西亚马逊人恶性疟原虫入侵红细胞中起重要作用。此外，这种寄生虫感染的易感性增加与该人群中的GPB S+变体相关。
Merozoites of Plasmodium falciparum invade through several pathways using different RBC receptors. Field isolates appear to use a greater variability of these receptors than laboratory isolates. Brazilian field isolates were shown to mostly utilize glycophorin A-independent invasion pathways via glycophorin B (GPB) and/or other receptors. The Brazilian population exhibits extensive polymorphism in blood group antigens, however, no studies have been done to relate the prevalence of the antigens that function as receptors for P. falciparum and the ability of the parasite to invade. Our study aimed to establish whether variation in the GYPB*S/s alleles influences susceptibility to infection with P. falciparum in the admixed population of Brazil. Two groups of Brazilian Amazonians from Porto Velho were studied: P. falciparum infected individuals (cases); and uninfected individuals who were born and/or have lived in the same endemic region for over ten years, were exposed to infection but have not had malaria over the study period (controls). The GPB Ss phenotype and GYPB*S/s alleles were determined by standard methods. Sixty two Ancestry Informative Markers were genotyped on each individual to estimate admixture and control its potential effect on the association between frequency of GYPB*S and malaria infection. GYPB*S is associated with host susceptibility to infection with P. falciparum; GYPB*S/GYPB*S and GYPB*S/GYPB*s were significantly more prevalent in the in the P. falciparum infected individuals than in the controls (69.87% vs. 49.75%; P<0.02). Moreover, population genetics tests applied on the GYPB exon sequencing data suggest that natural selection shaped the observed pattern of nucleotide diversity. Epidemiological and evolutionary approaches suggest an important role for the GPB receptor in RBC invasion by P. falciparum in Brazilian Amazons. Moreover, an increased susceptibility to infection by this parasite is associated with the GPB S+ variant in this population.
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作者：
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通讯作者：
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