Fu Katherine Yih-Jia, Zamudio Roxana, Henderson-Frost Jo, Almuedo Alex, Steinberg Hannah, Clipman Steven Joseph, Duran Gustavo, Marcus Rachel, Crawford Thomas, Alyesh Daniel, Colanzi Rony, Flores Jorge, Gilman Robert Hugh, Bern Caryn
Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States of America.
Department of Genetics, University of Leicester, Leicester, United Kingdom.
Rev Soc Bras Med Trop. 2017 Jul-Aug;50(4):516-523. doi: 10.1590/0037-8682-0015-2017.
: Trypanosoma cruzi (Tc) infection is usually acquired in childhood in endemic areas, leading to Chagas disease, which progresses to Chagas cardiomyopathy in 20-30% of infected individuals over decades. The pathogenesis of Chagas cardiomyopathy involves the host inflammatory response to T. cruzi, in which upstream caspase-1 activation prompts the cascade of inflammatory chemokines/cytokines, cardiac remodeling, and myocardial dysfunction. The aim of the present study was to examine the association of two caspase-1 single nucleotide polymorphisms (SNPs) with cardiomyopathy.
: We recruited infected (Tc+, n = 149) and uninfected (Tc-, n = 87) participants in a hospital in Santa Cruz, Bolivia. Cardiac status was classified (I, II, III, IV) based on Chagas cardiomyopathy-associated electrocardiogram findings and ejection fractions on echocardiogram. Genotypes were determined using Taqman probes via reverse transcription-polymerase chain reaction of peripheral blood DNA. Genotype frequencies were analyzed according to three inheritance patterns (dominant, recessive, additive) using logistic regression adjusted for age and sex.
: The AA allele for the caspase-1 SNP rs501192 was more frequent in Tc+ cardiomyopathy (classes II, III, IV) patients compared to those with a normal cardiac status (class I) [odds ratio (OR) = -2.18, p = 0.117]. This trend approached statistical significant considering only Tc+ patients in class I and II (OR = -2.64, p = 0.064).
: Caspase-1 polymorphisms may play a role in Chagas cardiomyopathy development and could serve as markers to identify individuals at higher risk for priority treatment.
克氏锥虫（Tc）感染通常在流行地区的儿童期获得，导致恰加斯病，在数十年间，20%-30%的感染者会发展为恰加斯心肌病。恰加斯心肌病的发病机制涉及宿主对克氏锥虫的炎症反应，其中上游半胱天冬酶-1的激活会引发炎症趋化因子/细胞因子的级联反应、心脏重塑和心肌功能障碍。本研究的目的是检验两个半胱天冬酶-1单核苷酸多态性（SNP）与心肌病的关联。
我们在玻利维亚圣克鲁斯的一家医院招募了受感染（Tc+，n = 149）和未受感染（Tc-，n = 87）的参与者。根据恰加斯心肌病相关的心电图结果和超声心动图上的射血分数对心脏状况进行分类（I、II、III、IV级）。通过对外周血DNA进行逆转录-聚合酶链反应，使用Taqman探针确定基因型。使用经年龄和性别调整的逻辑回归，根据三种遗传模式（显性、隐性、加性）分析基因型频率。
与心脏状况正常（I级）的患者相比，Tc+心肌病（II、III、IV级）患者中半胱天冬酶-1 SNP rs501192的AA等位基因更为常见[比值比（OR）=-2.18，p = 0.117]。仅考虑I级和II级的Tc+患者时，这一趋势接近统计学显著性（OR = -2.64，p = 0.064）。
半胱天冬酶-1多态性可能在恰加斯心肌病的发展中起作用，并可作为识别优先治疗高风险个体的标志物。
