Regional Medical Research Centre (ICMR), Bhubaneswar 751023, Orissa, India.
Infect Genet Evol. 2010 Mar;10(2):337-41. doi: 10.1016/j.meegid.2010.01.009. Epub 2010 Feb 1.
To explore the hypothesis that angiotensin II may play a role in the susceptibility to cerebral malaria (CM), we performed a genetic association study of malaria patients in Orissa, India analyzing three SNPs (ACE2 C-->T, iNOS C-->T, eNOS Glu-->Asp) and two I/D polymorphisms (ACE I/D and IL-4 B1/B2). Our results showed that the 'D' allele of ACE I/D polymorphism, responsible for increased Ang II production had a significant association with mild malaria and the ACE2 C-->T substitution had gender specific effect of possibly reduced expression of ACE2 in presence of 'T' allele in women leading to increased level of Ang II and hence protection against CM. Combined genotype analysis of eNOS Glu-->Asp substitution responsible for increased NO production in Plasmodium falciparum infected individuals and ACE I/D polymorphism also showed stronger association of (Glu-Asp+Asp-Asp/ID+DD) genotypes with mild malaria (P<0.0001). Whether by its antiplasmodial activity and/or by some unknown mechanisms, Ang II protects from susceptibility to cerebral malaria remains to be investigated. These genetic findings may contribute to the understanding of malaria pathogenesis.
为了探究血管紧张素 II 可能在脑型疟疾易感性中发挥作用的假说，我们在印度奥里萨邦进行了一项疟疾患者的遗传关联研究，分析了三个单核苷酸多态性（ACE2 C-->T、iNOS C-->T、eNOS Glu-->Asp）和两个插入/缺失多态性（ACE I/D 和 IL-4 B1/B2）。我们的研究结果表明，ACE I/D 多态性的“D”等位基因，负责增加血管紧张素 II 的产生，与轻度疟疾显著相关，ACE2 C-->T 取代在女性中可能导致 ACE2 表达减少，从而导致 Ang II 水平升高，从而对脑型疟疾产生保护作用。与 eNOS Glu-->Asp 取代相关的、负责增加疟原虫感染个体中一氧化氮产生的联合基因型分析，以及 ACE I/D 多态性也显示，Glu-Asp+Asp-Asp/ID+DD 基因型与轻度疟疾的关联更强（P<0.0001）。血管紧张素 II 是通过其抗疟原虫活性和/或通过一些未知机制来保护免受脑型疟疾易感性的影响，这仍有待研究。这些遗传发现可能有助于理解疟疾的发病机制。
