Malaria and Vector Research Group (MVRG), Biotechnology Research Center (BRC ), Pasteur Institute of Iran, Tehran, Iran.
Cell J. 2013 Summer;15(2):182-9. Epub 2013 Jul 2.
Different studies have shown an association of TLR4 polymorphisms with susceptibility/resistance to malaria disease. In the current immunogenetic study, we assessed the TLR4 genotypes formed by the two common single nucleotide polymorphisms (SNPs) (Asp299Gly and Thr399Ile) in the co-segregate state in Baluchi Plasmodium falciparum infected and healthy populations from malaria hypoendemic areas of Iran. The study was performed to evaluate the distribution and correlation of TLR4 co-segregating genotypes in patients with mild malaria. Moreover, the frequency of these genotypes was compared with reported results from other populations in similar or contrasting malaria settings around the world.
In this case control study, the presence of 2 SNPs in the TLR4 gene (Asp299Gly and Thr399Ile) were analyzed in 350 Baluchi patients with mild malaria and 350 unrelated healthy controls by using polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) techniques followed by sequencing analysis. Differences in the TLR4 co-segregate genotype frequencies among the studied group were determined by Fisher's exact test.
Although the distribution of the two commonly co-segregating TLR4 genotypes presented a diverse and distinct pattern in the Baluchi population, no significant difference was detected between the cases and controls (p>0.05). A lower frequency of TLR4 Asp299Gly/Thr399Thr was observed in Baluchis with mild malaria compared to African populations (p< 0.05).
Differences in the co-segregation patterns of TLR4 Asp299Gly/Thr399Ile genotypes in the Baluchi population compared to other malaria endemic populations may suggest different local evolutionary pressure on TLR4 polymorphisms by malaria in this region. The higher frequency of Asp299Gly/Thr399Ile genotypes among the Baluchi population compared with the African population (p< 0.05) which suffers from a larger number of severe cases might suggest that this genotype has a role in protecting against severe malaria. These findings are useful for further understanding the pathogenesis of severe malaria.
不同的研究表明 TLR4 多态性与疟疾易感性/抗性有关。在当前的免疫遗传学研究中，我们评估了在伊朗疟疾低度流行地区的感染和健康人群中，TLR4 两个常见单核苷酸多态性（SNP）（Asp299Gly 和 Thr399Ile）的共分离状态的 TLR4 基因型。该研究旨在评估轻度疟疾患者中 TLR4 共分离基因型的分布和相关性。此外，还将这些基因型的频率与来自世界各地类似或对比疟疾环境中的其他人群的报道结果进行了比较。
在这项病例对照研究中，采用聚合酶链反应/限制性片段长度多态性（PCR/RFLP）技术结合测序分析，检测了 350 名轻度疟疾的巴尔奇患者和 350 名无关健康对照者 TLR4 基因中的 2 个 SNP（Asp299Gly 和 Thr399Ile）的存在。通过 Fisher 确切检验确定研究组中 TLR4 共分离基因型频率的差异。
尽管巴尔奇人群中两种常见的共分离 TLR4 基因型的分布呈现出多样化和独特的模式，但病例组和对照组之间没有发现显著差异（p>0.05）。与非洲人群相比，巴尔奇轻度疟疾患者的 TLR4 Asp299Gly/Thr399Thr 频率较低（p<0.05）。
与其他疟疾流行地区的人群相比，巴尔奇人群中 TLR4 Asp299Gly/Thr399Ile 基因型的共分离模式存在差异，这可能表明该地区疟疾对 TLR4 多态性施加了不同的局部进化压力。与非洲人群（p<0.05）相比，巴尔奇人群中 Asp299Gly/Thr399Ile 基因型的频率较高，而非洲人群中严重病例较多，这表明这种基因型在预防严重疟疾方面发挥了作用。这些发现有助于进一步了解严重疟疾的发病机制。
