Association of the endothelial protein C receptor (PROCR) rs867186-G allele with protection from severe malaria.
Association of the endothelial protein C receptor (PROCR) rs867186-G allele with protection from severe malaria.
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DOI：
10.1186/1475-2875-13-105
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发表时间：
2014-03-17
期刊：
影响因子：
3
通讯作者：
Ohashi J
中科院分区：
文献类型：
--
作者：
Naka I;Patarapotikul J;Hananantachai H;Imai H;Ohashi J
恶性疟原虫感染的红细胞与微血管内皮细胞的细胞粘附是重症疟疾的显著特征。由内皮蛋白C受体基因（PROCR）编码的内皮蛋白C受体（EPCR）最近被鉴定为含有结构域盒（DC）8和13的特异性恶性疟原虫红细胞膜蛋白1（PfEMP 1）亚型的内皮受体。PROCR rs 867186-G等位基因（EPCR第219位丝氨酸-甘氨酸取代; 219 Gly）已显示与血浆可溶性EPCR（sEPCR）水平较高相关。在这项研究中，在泰国人群中检查了PROCR rs 867186与严重疟疾的关联。共有707名泰国恶性疟原虫疟疾患者（341名重度疟疾患者和336名轻度疟疾患者）进行了rs 867186基因分型。为了评估PROCR rs 867186与严重疟疾的关联，评估了三种模型（显性、隐性和等位基因）。估计PROCR基因编码序列的非同义和同义置换率。rs 867186-GG基因型与预防严重疟疾显著相关（P值= 0.026;比值比= 0.33; 95%置信区间= 0.12-0.90）。进化分析没有提供任何证据表明强阳性选择作用于PROCR基因。rs 867186-GG基因型与预防严重疟疾显著相关。目前的研究结果表明，PfEMP 1-EPCR相互作用，可以介导细胞粘附和/或减少细胞保护和抗炎作用，是至关重要的严重疟疾的发病机制。
Cytoadhesion of Plasmodium falciparum-infected erythrocytes to endothelial cells in microvessels is a remarkable characteristic of severe malaria. The endothelial protein C receptor (EPCR), encoded by the endothelial protein C receptor gene (PROCR), has recently been identified as an endothelial receptor for specific P. falciparum erythrocyte membrane protein 1 (PfEMP1) subtypes containing domain cassettes (DCs) 8 and 13. The PROCR rs867186-G allele (serine-to-glycine substitution at position 219 of EPCR; 219Gly) has been shown to be associated with higher levels of plasma soluble EPCR (sEPCR). In this study, the association of PROCR rs867186 with severe malaria is examined in Thai population. A total of 707 Thai patients with P. falciparum malaria (341 with severe malaria and 336 with mild malaria) were genotyped for rs867186. To assess the association of PROCR rs867186 with severe malaria, three models (dominant, recessive and allelic) were evaluated. The rates of non-synonymous and synonymous substitutions were estimated for the coding sequence of the PROCR gene. The rs867186-GG genotype was significantly associated with protection from severe malaria (P-value = 0.026; odds ratio = 0.33; 95% confidence interval = 0.12–0.90). Evolutionary analysis provided no evidence of strong positive selection acting on the PROCR gene. The rs867186-GG genotype showed significant association with protection from severe malaria. The present results suggest that PfEMP1–EPCR interaction, which can mediate cytoadhesion and/or reduce cytoprotective and anti-inflammatory effects, is crucial to the pathogenesis of severe malaria.
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DOI：
10.1073/pnas.1120455109
发表时间：
2012-06-26
影响因子：
11.1
作者：
Lavstsen, Thomas;Turner, Louise;Theander, Thor G.
通讯作者：
Theander, Thor G.
影响因子：
3.4
作者：
Guizetti J;Scherf A
通讯作者：
Scherf A
影响因子：
5.3
作者：
Ireland, H;Konstantoulas, CJ;Kurosawa, S
通讯作者：
Kurosawa, S
DOI：
10.1161/atvbaha.109.191551
发表时间：
2009-11-01
影响因子：
8.7
作者：
Ireland, Helen A.;Cooper, Jackie A.;Humphries, Stephen E.
通讯作者：
Humphries, Stephen E.
影响因子：
--
作者：
Kallel C;Cohen W;Saut N;Blankenberg S;Schnabel R;Rupprecht HJ;Bickel C;Munzel T;Tregouet DA;Morange PE
通讯作者：
Morange PE