恰加斯病是由拉丁美洲特有的原生动物克氏锥虫引起的终生感染,并在世界范围内出现。原发性感染后几十年,20-30%的感染者发展为慢性恰加斯心肌病(CCC),而其他人则无症状。CCC发病机制复杂,但与导致组织损伤的持续促炎反应有关。因此,IL-10水平可能在CCC病因中具有决定性作用。对拉丁美洲人群的研究已经解决了IL-10的遗传变异与发展为CCC的风险之间的关联,结果不一致。我们进行了一项病例对照研究,以探讨IL-10-1082G>A(rs18008969),-819C>T(rs1800871),-592A>C(rs1800872)多态性和CCC在阿根廷布宜诺斯艾利斯一家医院就诊的人群中。接下来,我们对文献进行了系统回顾,并结合现有研究和以往研究进行了荟萃分析,以进一步研究这种关联.
我们的病例对照研究包括122例慢性克氏锥虫感染患者,包括64例任何程度的CCC患者和58例无症状患者。IL-10-1082G基因分型>A,-819C>T,-592A>C多态性通过跨越三个多态性位点的区域的毛细管测序进行,并进行单变量和多变量统计分析。英文数据库,截至2021年12月,在西班牙语和葡萄牙语中搜索了与这些多态性和恰加斯病有关的论文。基于随机效应模型对所选文献和我们的研究进行了元分析。
在我们的队列中,我们发现-819rs1800871的TT基因型和-592rs1800872的AA基因型与显性模式下的CCC(OR=5.00;95CI=1.12-23.87P=0.04)和隐性模式(OR=5.37;95CI=1.12-25.68;P=0.03)之间存在显著关联。在三个多态性位置所符合的基因型中,纯合基因型ATA与CCC风险增加显著相关.754例和385例对照的荟萃分析结果表明,根据显性模型,-819C>T的TT基因型与CCC风险增加相关(OR=1.13;95%CI=1.02-1.25;P=0.03)。
-819rs1800871的基因型TT有助于对CCC的遗传易感性,使得该多态性成为包括在一组疾病进展的预测性生物标志物中的合适的候选者。
Chagas disease is a lifelong infection caused by the protozoa Trypanosoma cruzi endemic in Latin-America and emergent worldwide. Decades after primary infection, 20-30% of infected people develop chronic Chagas cardiomyopathy (CCC) while the others remain asymptomatic. CCC pathogenesis is complex but associated with sustained pro-inflammatory response leading to tissue damage. Hence, levels of IL-10 could have a determinant role in CCC etiology. Studies with Latin-American populations have addressed the association of genetic variants of IL-10 and the risk of developing CCC with inconsistent results. We carried out a
case control study to explore the association between IL-10-1082G>A (rs18008969), -819C>T (rs1800871), -592A>C (rs1800872) polymorphisms and CCC in a population attending a hospital in Buenos Aires Argentina. Next, a systematic review of the literature and a meta-analysis were conducted combining present and previous studies to further study this association.
Our
case control study included 122 individuals with chronic T. cruzi infection including 64 patients with any degree of CCC and 58 asymptomatic individuals. Genotyping of IL-10 -1082G>A, -819C>T, -592A>C polymorphisms was performed by capillary sequencing of the region spanning the three polymorphic sites and univariate and multivariate statistical analysis was undertaken. Databases in English, Spanish and Portuguese language were searched for papers related to these polymorphisms and Chagas disease up to December 2021. A metanalysis of the selected literature and our study was performed based on the random effect model.
In our cohort, we found a significant association between TT genotype of -819 rs1800871 and AA genotype of -592 rs1800872 with CCC under the codominant (OR=5.00; 95%CI=1.12-23.87 P=0,04) and the recessive models (OR=5.37; 95%CI=1.12-25.68; P=0,03). Of the genotypes conformed by the three polymorphic positions, the homozygous genotype ATA was significantly associated with increased risk of CCC. The results of the meta-analysis of 754 cases and 385 controls showed that the TT genotype of -819C>T was associated with increased CCC risk according to the dominant model (OR=1.13; 95% CI=1.02-1.25; P=0,03).
The genotype TT at -819 rs1800871 contributes to the genetic susceptibility to CCC making this polymorphism a suitable candidate to be included in a panel of predictive biomarkers of disease progression.