TOLLIP gene variant is associated with Plasmodium vivax malaria in the Brazilian Amazon
TOLLIP gene variant is associated with Plasmodium vivax malaria in the Brazilian Amazon
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DOI：
10.1186/s12936-017-1754-7
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发表时间：
2017-03-13
期刊：
影响因子：
3
通讯作者：
Ramasawmy, Rajendranath
中科院分区：
文献类型：
--
作者：
Brasil, Larissa W.;Barbosa, Laila R. A.;Ramasawmy, Rajendranath
背景：toll相互作用蛋白是TLR信号级联中的负调节因子，特别是通过阻碍TLR2和TLR4途径。最近，TOLLIP被证明可以调节人类TLR信号通路。据报道，两种常见的TOLLIP多态性（rss5743899和rs3750920）影响IL-6、TNF和IL-10的表达。在本研究中，研究了TOLLIP变异与巴西亚马逊地区间日疟原虫疟疾的关系。方法：本队列研究在巴西西部亚马逊地区的卡雷罗市和马瑙斯市进行。共有319例间日疟原虫疟疾患者和263例既往无疟疾史的健康对照者被纳入研究。使用QIAamp (R) DNA迷你试剂盒，根据制造商建议的方案，从滤纸上收集的血液中提取基因组DNA。采用PCR-RFLP方法对TOLLIP基因rss5743899和rs3750920多态性进行分型。结果：rs3750920 T等位基因纯合子个体患疟疾的风险是C等位基因纯合子个体的两倍（OR 2.0 [95% CI 1.23-3.07]; p = 0.004）。在优势模型中，携带C等位基因的个体对疟疾具有保护作用，将携带C等位基因的个体与携带T等位基因的个体进行比较，差异非常显著（OR 0.52 [95% CI 0.37-0.76]; p = 0.0006）。两个多态性之间的连锁不平衡较弱（r2 = 0.037； D' = 0.27）。结论：这些发现提示参与tlrs通路的基因可能参与了疟疾的易感性。TOLLIP rs3750920t等位基因与疟疾易感性的关联进一步证明，免疫应答基因的遗传变异可能使个体易患疟疾。
Background: Toll-interacting protein is a negative regulator in the TLR signaling cascade, particularly by impeding the TLR2 and, TLR4 pathway. Recently, TOLLIP was shown to regulate human TLR signaling pathways. Two common TOLLIP polymorphisms (rs5743899 and rs3750920) were reported to be influencing IL-6, TNF and IL-10 expression. In this study, TOLLIP variants were investigated to their relation to Plasmodium vivax malaria in the Brazilian Amazon.Methods: This cohort study was performed in the municipalities of Careiro and, Manaus, in Western Brazilian Amazon. A total of 319 patients with P. vivax malaria and, 263 healthy controls with no previous history of malaria were included in the study. Genomic DNA was extracted from blood collected on filter paper, using the QIAamp (R) DNA Mini Kit, according to the manufacturer's suggested protocol. The rs5743899 and rs3750920 polymorphisms of the TOLLIP gene were typed by PCR-RFLP.Results: Homozygous individuals for the rs3750920 T allele gene had twice the risk of developing malaria when compared to individuals homozygous for the C allele (OR 2.0 [95% CI 1.23-3.07]; p = 0.004). In the dominant model, carriers the C allele indicates protection to malaria, carriers of the C allele were compared to individuals with the T allele, and the difference is highly significant (OR 0.52 [95% CI 0.37-0.76]; p = 0.0006). The linkage disequilibrium between the two polymorphisms was weak (r2 = 0.037; D' = 0.27).Conclusions: These findings suggest that genes involved in the TLRs-pathway may be involved in malaria susceptibility. The association of the TOLLIP rs3750920 T allele with susceptibility to malaria further provides evidence that genetic variations in immune response genes may predispose individuals to malaria.