Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.
Malar J. 2013 Jan 8;12:9. doi: 10.1186/1475-2875-12-9.
Regulatory T cells (Tregs) are a subset of T cells that play an important role in modulating T effector responses during infectious challenges. The aim of this study was to evaluate possible associations between regulatory gene polymorphisms and the risk of uncomplicated malaria and the control of Plasmodium falciparum parasite density levels.
Twelve regulatory single nucleotide polymorphisms (SNPs) in the promoter regions of FOXP3 (ss270137548, rs11091253), IL10RA (rs56356146, rs7925112), IL10RB (rs8178433, rs8178435, rs999788), STAT6 (rs3024941, rs3024943, rs3024944) and TNFRSF18 (ss2080581728, rs3753344) were genotyped in a cohort of Congolese children. Studied subjects were followed up (passively) during one year. The children who experienced one or several clinical episodes were genotyped as "uncomplicated malaria" group (n=179) and those children who did not experience any episode were genotyped as "asymptomatic children" group (n=138).
The prevalence of rs3024944CC genotype of STAT6 was significantly higher in the group of asymptomatic children compared to that of uncomplicated malaria (P=0.003). Similarly, the minor allele rs3024944C was more prevalent in the group of asymptomatic children (P=0.019). Two novel SNPs were observed including -163T/G (ss491228441) in IL10RA gene and -163C/T (ss491228440) in TNFRSF18 gene. The genotype ss491228441TT and the minor allele ss491228441G of the IL10RA were more frequent in the group of asymptomatic children (P=0.006 and P=0.007, respectively). The genotype rs11091253CT of the FOXP3 was associated with high parasite density levels. In addition, a new promoter IL10RA variant (ss491228441) contributes to shield against mild malaria.
The study indicated that the STAT6 promoter polymorphism rs3024944 was associated with uncomplicated malaria, whereas the FOXP3 promoter variant rs11091253 was associated with significant P. falciparum parasitaemia levels. These genetic data may contribute to the understanding of molecular mechanisms that regulate immune response to P. falciparum infections.
调节性 T 细胞（Tregs）是 T 细胞的一个亚群，在调节感染性挑战期间的 T 效应应答方面发挥着重要作用。本研究旨在评估调节基因多态性与无并发症疟疾的风险和控制间的可能关联，以及疟原虫密度水平。
对刚果儿童队列中的 FOXP3（ss270137548、rs11091253）、IL10RA（rs56356146、rs7925112）、IL10RB（rs8178433、rs8178435、rs999788）、STAT6（rs3024941、rs3024943、rs3024944）和 TNFRSF18（ss2080581728、rs3753344）的 12 个调节性单核苷酸多态性（SNP）在启动子区域进行基因分型。对研究对象进行为期一年的（被动）随访。出现一个或多个临床发作的儿童被基因分型为“无并发症疟疾”组（n=179），未出现任何发作的儿童被基因分型为“无症状儿童”组（n=138）。
与无并发症疟疾组相比，无症状儿童组的 STAT6 基因 rs3024944CC 基因型的患病率显著更高（P=0.003）。同样，次要等位基因 rs3024944C 在无症状儿童组中更为常见（P=0.019）。观察到两个新的 SNP，包括 IL10RA 基因中的-163T/G（ss491228441）和 TNFRSF18 基因中的-163C/T（ss491228440）。IL10RA 的基因型 ss491228441TT 和 ss491228441G 等位基因在无症状儿童组中更为常见（P=0.006 和 P=0.007）。FOXP3 的 rs11091253CT 基因型与高寄生虫密度水平相关。此外，新的 IL10RA 启动子变体（ss491228441）有助于预防轻度疟疾。
该研究表明，STAT6 启动子多态性 rs3024944 与无并发症疟疾相关，而 FOXP3 启动子变体 rs11091253 与显著的疟原虫寄生虫密度水平相关。这些遗传数据可能有助于理解调节对疟原虫感染免疫应答的分子机制。
