Aix-Marseille Université, INSERM, GIMP UMR_S906, Faculté de médecine, 27 bd Jean Moulin, Marseille, cedex 05 13385, France.
BMC Infect Dis. 2013 Dec 12;13:587. doi: 10.1186/1471-2334-13-587.
Chagas disease, caused by the protozoan Trypanosoma cruzi is endemic in Latin America. Thirty percent of infected individuals develop chronic Chagas cardiomyopathy (CCC), an inflammatory dilated cardiomyopathy that is, by far, the most important clinical consequence of T. cruzi infection. The others remain asymptomatic (ASY). A possible genetic component to disease progression was suggested by familial aggregation of cases and the association of markers of innate and adaptive immunity genes with CCC development. Migration of Th1-type T cells play a major role in myocardial damage.
Our genetic analysis focused on CCR5, CCL2 and MAL/TIRAP genes. We used the Tag SNPs based approach, defined to catch all the genetic information from each gene. The study was conducted on a large Brazilian population including 315 CCC cases and 118 ASY subjects.
The CCL2rs2530797A/A and TIRAPrs8177376A/A were associated to an increase susceptibility whereas the CCR5rs3176763C/C genotype is associated to protection to CCC. These associations were confirmed when we restricted the analysis to severe CCC, characterized by a left ventricular ejection fraction under 40%.
Our data show that polymorphisms affecting key molecules involved in several immune parameters (innate immunity signal transduction and T cell/monocyte migration) play a role in genetic susceptibility to CCC development. This also points out to the multigenic character of CCC, each polymorphism imparting a small contribution. The identification of genetic markers for CCC will provide information for pathogenesis as well as therapeutic targets.
由原生动物克氏锥虫引起的恰加斯病在拉丁美洲流行。30%的感染者会发展为慢性恰加斯心肌病（CCC），这是迄今为止克氏锥虫感染的最重要的临床后果，是一种炎症性扩张型心肌病。其余的人则没有症状（ASY）。家族聚集病例和固有及适应性免疫基因标志物与 CCC 发展的相关性提示疾病进展可能存在遗传成分。Th1 型 T 细胞的迁移在心肌损伤中起主要作用。
我们的遗传分析集中在 CCR5、CCL2 和 MAL/TIRAP 基因上。我们使用了基于标签 SNP 的方法，旨在捕捉每个基因的所有遗传信息。该研究在一个包括 315 例 CCC 病例和 118 例 ASY 受试者的大型巴西人群中进行。
CCL2rs2530797A/A 和 TIRAPrs8177376A/A 等位基因与易感性增加相关，而 CCR5rs3176763C/C 基因型与 CCC 的保护相关。当我们将分析限制在特征为左心室射血分数低于 40%的严重 CCC 时，这些关联得到了证实。
我们的数据表明，影响参与多个免疫参数（固有免疫信号转导和 T 细胞/单核细胞迁移）的关键分子的多态性在 CCC 发展的遗传易感性中起作用。这也指出了 CCC 的多基因特征，每个多态性都有微小的贡献。CCC 遗传标志物的鉴定将为发病机制和治疗靶点提供信息。
