Influence of Angiotensin-converting Enzyme Insertion/Deletion Gene Polymorphism in Progression of Chagas Heart Disease

Abstract INTRODUCTION: Chagas disease (CD) is a neglected disease caused by the parasite Trypanosoma cruzi. One-third of infected patients will develop the cardiac form, which may progress to heart failure (HF). However, the factors that determine disease progression remain unclear. Increased angiotensin II activity is a key player in the pathophysiology of HF. A functional polymorphism of the angiotensin-converting enzyme (ACE) gene is associated with plasma enzyme activity. In CD, ACE inhibitors have beneficial effects supporting the use of this treatment in chagasic cardiomyopathy. METHODS: We evaluated the association of ACE I/D polymorphism with HF, performing a case-control study encompassing 343 patients with positive serology for CD staged as non-cardiomyopathy (stage A; 100), mild (stage B1; 144), and severe (stage C; 99) forms of Chagas heart disease. For ACE I/D genotyping by PCR, groups were compared using unconditional logistic regression analysis and adjusted for nongenetic covariates: age, sex, and trypanocidal treatment. RESULTS: A marginal, but not significant (p=0.06) higher prevalence of ACE I/D polymorphism was observed in patients in stage C compared with patients in stage A. Patients in stage C (CD with HF), were compared with patients in stages A and B1 combined into one group (CD without HF); DD genotype/D carriers were prevalent in the HF patients (OR = 2; CI = 1.013.96; p = 0.04). CONCLUSIONS: Our results of this cohort study, comprising a population from the Northeast region of Brazil, suggest that ACE I/D polymorphism is more prevalent in the cardiac form of Chagas disease with HF.

摘要 引言：恰加斯病（Chagas disease）是由克氏锥虫（Trypanosoma cruzi）引发的一种被忽视的寄生虫病。约三分之一的感染者会发展为心脏型恰加斯病，病情可进展为心力衰竭（HF）。然而，目前尚不明确决定疾病进展的相关因素。血管紧张素II活性升高是心力衰竭病理生理过程中的关键环节。血管紧张素转换酶（ACE）基因的功能多态性与血浆酶活性相关。在恰加斯病患者中，血管紧张素转换酶抑制剂可产生有益疗效，支持其在恰加斯心肌病中的临床应用。
方法：本研究开展一项病例对照研究，纳入343例恰加斯病血清学阳性患者，按病情分期分为非心肌病组（A期；100例）、轻度恰加斯心脏病组（B1期；144例）及重度恰加斯心脏病组（C期；99例），旨在探讨ACE I/D多态性与心力衰竭的关联。采用聚合酶链反应（PCR）进行ACE I/D基因分型，通过无条件logistic回归分析对各组进行比较，并校正年龄、性别、抗锥虫治疗等非遗传协变量的影响。
结果：与A期患者相比，C期患者的ACE I/D多态性患病率呈边际升高趋势，但未达到统计学显著性（p=0.06）。将A期与B1期患者合并为无心力衰竭的恰加斯病对照组，与合并心力衰竭的C期患者进行比较后发现，DD基因型/D等位基因携带者在心力衰竭患者中更为常见（比值比（OR）=2；置信区间（CI）=1.01~3.96；p=0.04）。
结论：这项针对巴西东北部人群的队列研究结果表明，ACE I/D多态性在合并心力衰竭的恰加斯病心脏型患者中患病率更高。