Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Malar J. 2012 Dec 7;11:409. doi: 10.1186/1475-2875-11-409.
Malaria is among the most prevalent parasitic diseases worldwide. In Brazil, malaria is concentrated in the northern region, where Plasmodium vivax accounts for 85% disease incidence. The role of genetic factors in host immune system conferring resistance/susceptibility against P. vivax infections is still poorly understood.
The present study investigates the influence of polymorphisms in 18 genes related to the immune system in patients with malaria caused by P. vivax. A total of 263 healthy individuals (control group) and 216 individuals infected by P. vivax (malaria group) were genotyped for 33 single nucleotide polymorphisms (SNPs) in IL1B, IL2, IL4, IL4R, IL6, IL8, IL10, IL12A, IL12B, IL12RB1, SP110, TNF, TNFRSF1A, IFNG, IFNGR1, VDR, PTPN22 and P2X7 genes. All subjects were genotyped with 48 ancestry informative insertion-deletion polymorphisms to determine the proportion of African, European and Amerindian ancestry. Only 13 SNPs in 10 genes with differences lower than 20% between cases and controls in a Poisson Regression model with age as covariate were further investigated with a structured population association test.
The IL1B gene -5839C > T and IL4R 1902A > G polymorphisms and IL12RB1 -1094A/-641C and TNF -1031 T/-863A/-857 T/-308 G/-238 G haplotypes were associated with malaria susceptibility after population structure correction (p = 0.04, p = 0.02, p = 0.01 and p = 0.01, respectively).
Plasmodium vivax malaria pathophysiology is still poorly understood. The present findings reinforce and increase our understanding about the role of the immune system in malaria susceptibility.
疟疾是全球最普遍的寄生虫病之一。在巴西，疟疾主要集中在北部地区，其中间日疟原虫（Plasmodium vivax）导致了 85%的病例。遗传因素在宿主免疫系统中对抵抗/易感性的影响仍知之甚少。
本研究调查了与免疫系统相关的 18 个基因中的多态性在感染间日疟原虫（Plasmodium vivax）的疟疾患者中的影响。对 263 名健康个体（对照组）和 216 名感染间日疟原虫的个体（疟疾组）进行了 33 个单核苷酸多态性（SNP）的基因分型，这些 SNP 位于 IL1B、IL2、IL4、IL4R、IL6、IL8、IL10、IL12A、IL12B、IL12RB1、SP110、TNF、TNFRSF1A、IFNG、IFNGR1、VDR、PTPN22 和 P2X7 基因中。所有研究对象均进行了 48 个祖先信息插入缺失多态性的基因分型，以确定非洲、欧洲和美洲印第安人祖先的比例。仅对病例与对照组之间差异低于 20%的 10 个基因中的 13 个 SNP 进行了进一步研究，采用包含年龄作为协变量的泊松回归模型进行分析，并进行了基于群体结构的关联测试。
IL1B 基因 -5839C>T 和 IL4R 1902A>G 多态性以及 IL12RB1-1094A/-641C 和 TNF-1031T/-863A/-857T/-308G/-238G 单倍型与校正群体结构后的疟疾易感性相关（p=0.04、p=0.02、p=0.01 和 p=0.01）。
间日疟原虫疟疾的发病机制仍知之甚少。本研究结果进一步证实并加深了我们对免疫系统在疟疾易感性中的作用的理解。
