Silva Pedro X, Aguiar Laura, Gaspar Marcos, Faustino Paula, Falcão Luiz M, Barbosa Mário, Bicho Manuel, Inácio Ângela
Genetics Laboratory, Faculty of Medicine of the University of Lisbon, Lisbon, PRT.
Associate Laboratory TERRA, Environmental Health Institute, Faculty of Medicine of the University of Lisbon, Lisbon, PRT.
Cureus. 2024 May 20;16(5):e60707. doi: 10.7759/cureus.60707. eCollection 2024 May.
Heart failure (HF) is a clinical syndrome characterized by cardinal symptoms that may be accompanied by signs. It results from structural and/or functional abnormalities of the heart leading to elevated intracardiac pressures and/or inadequate cardiac output at rest and/or during exercise. The prevalence of iron deficiency and anemia justifies the current guidelines recommendation of screening. Genes , , and are involved in oxidative mechanisms, iron metabolism, and hematologic homeostasis. This study investigates the contribution of variants Hp1/2 (), I/D (), C677T (), C282Y and H63D (), and C242T () to the development of HF, either independently or in epistasis.
We used a database of 389 individuals, 143 HF patients, and 246 healthy controls. Genotypes were characterized through PAGE electrophoresis, PCR, PCR-RFLP, and multiplex-ARMS. Data analysis was performed with the SPSS® 26.0 software (IBM Corp., Armonk, NY).
We observed a significant association between the gene and HF predisposition. The presence of allele T and genotype CT constituted risk, while genotype CC granted protection. Epistatic interactions revealed risk between genotype II of the gene and genotypes CC ( or HH ( of the gene. Risk was also observed for interactions between genotype CC ()and genotypes 2-2 (, CT (), or HH (.
We concluded that genes , , and contribute to the susceptibility for HF, individually or in epistasis. This study contributes to the clarification of the role that genes involved in oxidative mechanisms and iron metabolism play in the physiopathology of HF. It is, therefore, a step forward in risk stratification and personalized medicine.
心力衰竭（HF）是一种临床综合征，其特征为主要症状，可能伴有体征。它由心脏的结构和/或功能异常引起，导致心腔内压力升高和/或静息和/或运动时心输出量不足。缺铁和贫血的患病率证明了当前指南中筛查建议的合理性。基因 、 、 和 参与氧化机制、铁代谢和血液学稳态。本研究调查了Hp1/2（）、I/D（）、C677T（）、C282Y和H63D（）以及C242T（）变体对HF发生发展的贡献，无论是独立作用还是上位作用。
我们使用了一个包含389名个体的数据库，其中143名HF患者和246名健康对照。通过PAGE电泳、PCR、PCR-RFLP和多重扩增不应变系统（ARMS）对基因型进行表征。使用SPSS® 26.0软件（IBM公司，纽约州阿蒙克）进行数据分析。
我们观察到 基因与HF易感性之间存在显著关联。等位基因T的存在和基因型CT构成风险，而基因型CC提供保护。上位相互作用揭示了 基因的基因型II与 基因的基因型CC（ 或HH（ 之间的风险。在基因型CC（）与基因型2-2（、CT（）或HH（ 之间的相互作用中也观察到风险。
我们得出结论，基因 、 、 和 单独或通过上位作用对HF易感性有影响。本研究有助于阐明参与氧化机制和铁代谢的基因在HF病理生理学中的作用。因此，这是在风险分层和个性化医疗方面向前迈出的一步。
