Malaria and Vector Research Group, Biotechnology Research Center, Institut Pasteur Iran, Tehran, Iran, Pasteur Avenue, POBOX 1316943551, Tehran, Iran.
Malar J. 2011 Apr 4;10:77. doi: 10.1186/1475-2875-10-77.
Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns and their activation leads to the induction of effector genes involving inflammatory cytokines that may have contribute to controlling parasite growth and disease pathogenesis. The current immunogenetic study was designed to analyse the key components of innate immunity, TLRs and TIRAP (Toll-interleukin-1 receptor domain-containing adaptor protein), also known as MAL (MYD88 adaptor-like), in Iranian patients with mild malaria.
The tlr-4 (D299G and T399I), tlr-9 (T-1486C and T-1237C) and tirap (S180L) genes were assessed in 640 Baluchi individuals (320 Plasmodium falciparum-infected and 320 non-infected, median age of 28 years) from malaria-endemic regions using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods.
Common tlr-4 SNPs and promoter SNPs of tlr-9 were distributed among P. falciparum-infected and non-infected groups (P > 0.05) that showed no association of these variants with mild clinical manifestation. The comparison of the tirap S180L genotypes between patients with mild malaria and those healthy individuals showed that the frequency of heterozygosity was significantly higher in infected than non-infected individuals (33.8 vs. 25.6; OR, 1.479; 95% CI, 1.051-2.081; P = 0.024). The result also revealed a significant association of tirap S180L (P < 0.05) with development of mild malaria, which is common in Baluchi populations, who are living in malaria hypoendemic region of Iran but not in African populations (0%-6%).
These data point towards the need for addressing the exact role of TLRs in contributing to human genetic factors in malaria susceptibility/resistance/severity within different malaria settings in the world.
Toll 样受体 (TLR) 识别病原体相关分子模式，其激活导致诱导涉及炎症细胞因子的效应基因，这些细胞因子可能有助于控制寄生虫生长和疾病发病机制。本研究旨在分析伊朗轻度疟疾患者固有免疫的关键成分，TLR 和 TIRAP（Toll-白细胞介素-1 受体域包含衔接蛋白），也称为 MAL（MYD88 衔接样）。
采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法，对来自疟疾流行地区的 640 名巴尔奇个体（320 名疟原虫感染和 320 名未感染，中位年龄 28 岁）进行 TLR-4（D299G 和 T399I）、TLR-9（T-1486C 和 T-1237C）和 TIRAP（S180L）基因检测。
TLR-9 常见的 SNP 和启动子 SNP 在疟原虫感染和未感染组中分布（P > 0.05），这些变异与轻度临床表现无关。轻度疟疾患者与健康个体之间 TIRAP S180L 基因型的比较显示，感染组杂合性频率明显高于未感染组（33.8%比 25.6%；OR，1.479；95%CI，1.051-2.081；P = 0.024）。结果还显示，TIRAP S180L 与轻度疟疾的发生显著相关（P < 0.05），这种相关性在伊朗疟疾低度流行地区的巴尔奇人群中很常见，但在非洲人群中并不常见（0%-6%）。
这些数据表明，需要在不同疟疾环境中，确定 TLR 在导致人类对疟疾易感性/抗性/严重程度的遗传因素中的具体作用。
