Machuca Mayra Alejandra, Suárez Edwin Uriel, Echeverría Luis Eduardo, Martín Javier, González Clara Isabel
Grupo de Inmunología y Epidemiología Molecular, GIEM, Facultad de Salud, Universidad Industrial de Santander, Bucaramanga, Colombia.
Grupo de Ciencias Cardiovasculares, Fundación Cardiovascular de Colombia, Floridablanca, Santander, Colombia.
Hum Immunol. 2014 Dec;75(12):1210-5. doi: 10.1016/j.humimm.2014.09.023. Epub 2014 Oct 12.
Chronic inflammation plays a major role in the tissue injury seen in the chronic chagasic cardiomyopathy. The CCR2 and CCR5 chemokine receptors are involved with the type of cellular infiltrate present in cardiac tissue and CCR5-gene variants were previously associated with this pathology.
This is a replication study in an independent cohort with larger sample size. Nine SNPs of CCR5 and CCR2 were typified to confirm the association previously found with Chagas disease. Evidence of association with severity was found for the A allele of rs1799864 of CCR2 (pad=0.02; OR=1.91, 95% CI=1.10-3.30), the T allele of the rs1800024 of CCR5 (pad=0.01; OR=1.95, 95% CI=1.13-3.38), and the HHF(∗)2 haplotype (p=0.03, OR=1.65, 95% CI=1.03-2.65). These results were replicated in the study combined with previous data. In this analysis it was replicated the allele T of rs2734648 (pad=0.009, OR=0.52, 95% CI=0.32-0.85) with protection. In addition, the allele G of rs1800023 (pad=0.043, OR=0.61, 95% CI=0.38-0.98), and the HHC haplotype (p=0.004, OR=0.62, 95% CI=0.44-0.86) were also associated with protection. In contrast, the allele A of rs1799864 of CCR2 (pad=0.009; OR=1.90, 95% CI=1.17-3.08); and the allele T of rs1800024 of CCR5 (pad=0.005, OR=1.98, 95% CI=1.22-3.23) were associated with greater severity. No evidence of association between symptomatic and asymptomatic patients was observed.
These results confirm that variants of CCR5 and CCR2 genes and their haplotypes are associated with the severity but not with susceptibility to develop chagasic cardiomyopathy.
慢性炎症在慢性恰加斯病性心肌病的组织损伤中起主要作用。CCR2和CCR5趋化因子受体与心脏组织中存在的细胞浸润类型有关，并且CCR5基因变异先前已与这种病理状况相关联。
这是一项在独立队列中进行的具有更大样本量的重复研究。对CCR5和CCR2的9个单核苷酸多态性（SNP）进行分型，以确认先前发现的与恰加斯病的关联。发现CCR2的rs1799864的A等位基因（pad = 0.02；比值比[OR]=1.91，95%可信区间[CI]=1.10 - 3.30）、CCR5的rs1800024的T等位基因（pad = 0.01；OR = 1.95，95% CI = 1.13 - 3.38）以及HHF(∗)2单倍型（p = 0.03，OR = 1.65，95% CI = 1.03 - 2.65）与疾病严重程度相关。这些结果在结合先前数据的研究中得到了重复验证。在该分析中，rs2734648的T等位基因（pad = 0.009，OR = 0.52，95% CI = 0.32 - 0.85）具有保护作用也得到了重复验证。此外，rs1800023的G等位基因（pad = 0.043，OR = 0.61，95% CI = 0.38 - 0.98）以及HHC单倍型（p = 0.004，OR = 0.62，95% CI = 0.44 - 0.86）也与保护作用相关。相反，CCR2的rs1799864的A等位基因（pad = 0.009；OR = 1.90，95% CI = 1.17 - 3.08）；以及CCR5的rs1800024的T等位基因（pad = 0.005，OR = 1.98，95% CI = 1.22 - 3.23）与更高的疾病严重程度相关。未观察到有症状和无症状患者之间存在关联的证据。
这些结果证实，CCR5和CCR2基因的变异及其单倍型与恰加斯病性心肌病的严重程度有关，但与发病易感性无关。
