INGEBI-CONICET, Buenos Aires, Argentina.
GIEM, Universidad Industrial de Santander, Bucaramanga, Colombia.
PLoS Negl Trop Dis. 2019 Jan 16;13(1):e0007033. doi: 10.1371/journal.pntd.0007033. eCollection 2019 Jan.
Several studies have proposed different genetic markers of susceptibility to develop chronic Chagas cardiomyopathy (CCC). Many genes may be involved, each one making a small contribution. For this reason, an appropriate approach for this problematic is to study a large number of single nucleotide polymorphisms (SNPs) in individuals sharing a genetic background. Our aim was to analyze two CCR2 and seven CCR5 SNPs and their association to CCC in Argentina. A case-control study was carried out in 480 T. cruzi seropositive adults from Argentinean Gran Chaco endemic region (Wichi and Creole) and patients from Buenos Aires health centres. They were classified according to the Consensus on Chagas-Mazza Disease as non-demonstrated (non-DC group) or demonstrated (DC group) cardiomyopathy, i.e. asymptomatic or with CCC patients, respectively. Since, after allelic analysis, 2 out of 9 studied SNPs did not fit Hardy-Weinberg equilibrium in the unaffected non-DC group from Wichi patients, we analyzed them as a separate population. Only rs1800024T and rs41469351T in CCR5 gene showed significant differences within non-Wichi population (Creole + patients from Buenos Aires centres), being the former associated to protection, and the latter to risk of CCC. No evidence of association was observed between any of the analyzed CCR2-CCR5 gene polymorphisms and the development of CCC; however, the HHE haplotype was associated with protection in Wichi population. Our findings support the hypothesis that CCR2-CCR5 genes and their haplotypes are associated with CCC; however, depending on the population studied, different associations can be found. Therefore, the evolutionary context, in which the genes or haplotypes are associated with diseases, acquires special relevance.
多项研究提出了不同的遗传易感性标志物，用于发展慢性恰加斯心肌病（CCC）。许多基因可能参与其中，每个基因的贡献都很小。因此，对于这个问题的恰当方法是在具有遗传背景的个体中研究大量的单核苷酸多态性（SNP）。我们的目的是分析两个 CCR2 和七个 CCR5 SNP 及其与阿根廷 CCC 的关联。在阿根廷大查科疫区（Wichi 和克里奥尔）的 480 名 T. cruzi 血清阳性成年人和布宜诺斯艾利斯保健中心的患者中进行了病例对照研究。他们根据 Chagas-Mazza 疾病共识分为未表现（非 DC 组）或表现（DC 组）心肌病，即无症状或伴有 CCC 的患者。由于在未受影响的非 DC 组的 Wichi 患者中，9 个研究 SNP 中有 2 个不符合 Hardy-Weinberg 平衡，因此我们将它们作为单独的人群进行分析。只有 CCR5 基因中的 rs1800024T 和 rs41469351T 在非 Wichi 人群（克里奥尔+来自布宜诺斯艾利斯中心的患者）中显示出显著差异，前者与保护相关，后者与 CCC 风险相关。在分析的任何 CCR2-CCR5 基因多态性与 CCC 的发展之间均未观察到关联；然而，在 Wichi 人群中，HHE 单倍型与保护相关。我们的研究结果支持 CCR2-CCR5 基因及其单倍型与 CCC 相关的假设；然而，根据所研究的人群，可能会发现不同的关联。因此，与疾病相关的基因或单倍型的进化背景获得了特殊的相关性。
