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Published on: February 7, 2018
Analysis of Genes Involved in Oxidative Stress and Iron Metabolism in Heart Failure: A Step Forward in Risk
Pedro X Silva1,2, Laura Aguiar2,3, Marcos Gaspar1,2,3
1Genetics Laboratory, Faculty of Medicine of the University of Lisbon, Lisbon, PRT.
Insights
Genetic variants in HP, ACE, MTHFR, HFE, and CYBA genes influence heart failure (HF) risk. MTHFR gene variants showed a significant association with HF predisposition, highlighting the role of these genes in HF development.
Area of Science:
- Genetics and Cardiovascular Disease
- Molecular Medicine
- Human Genomics
Background:
- Heart failure (HF) is a complex clinical syndrome arising from cardiac structural or functional abnormalities.
- Iron deficiency and anemia are prevalent in HF, necessitating screening as per current guidelines.
- Specific genes (HP, ACE, MTHFR, HFE, CYBA) are implicated in oxidative stress, iron metabolism, and hematologic balance, potentially influencing HF development.
Purpose of the Study:
- To investigate the independent and epistatic contributions of variants in HP, ACE, MTHFR, HFE, and CYBA genes to heart failure susceptibility.
- To explore the role of genetic variations in oxidative mechanisms and iron metabolism in the pathophysiology of HF.
Main Methods:
- Genotyping of 389 individuals (143 HF patients, 246 controls) using PAGE electrophoresis, PCR, PCR-RFLP, and multiplex-ARMS.
- Statistical analysis of genetic data using SPSS® 26.0 software.
Main Results:
- A significant association was found between MTHFR gene variants and HF predisposition, with allele T and genotype CT increasing risk, while genotype CC offered protection.
- Epistatic interactions indicated increased risk between ACE gene (genotype II) and HFE gene (genotypes CC or HH).
- Further risk was observed for interactions involving CYBA (genotype CC) with HP (genotype 2-2), MTHFR (genotype CT), or HFE-H63D (genotype HH).
Conclusions:
- Genes HP, ACE, MTHFR, HFE, and CYBA contribute to HF susceptibility, both individually and through epistatic interactions.
- This research clarifies the role of genes involved in oxidative processes and iron metabolism in HF pathophysiology.
- Findings represent a step towards improved risk stratification and personalized medicine approaches for heart failure.
Introduction:
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 HP, ACE, MTHFR, HFE, and CYBA are involved in oxidative mechanisms, iron metabolism, and hematologic homeostasis. This study investigates the contribution of variants Hp1/2 (HP), I/D (ACE), C677T (MTHFR), C282Y and H63D (HFE), and C242T (CYBA) to the development of HF, either independently or in epistasis.
Methods:
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).
Results:
We observed a significant association between the MTHFR 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 ACE gene and genotypes CC (C282Y) or HH (H63D) of the HFE gene. Risk was also observed for interactions between genotype CC (CYBA)and genotypes 2-2 (HP), CT (MTHFR), or HH (HFE-H63D).
Conclusion:
We concluded that genes HP, ACE, MTHFR, HFE, and CYBA 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.
