Investigação de alterações citogenéticas moleculares em pacientes pediátricos portadores de doenças cardiovasculares

Abstract

Introduction: Congenital heart diseases (CHD) may impact the cardiorespiratory system with a variety of systematic repercussions and occur in approximately 1% of live births. Genetic factors influence their etiology. There is a lack of data on CHD in Manaus-Amazonas, reinforcing the importance of its characterization. Objective: The objective of this study was to investigate and characterize cytogenetic alterations using the MLPA technique and the genotypes of single-nucleotide variants (SNVs) associated with cardiovascular diseases and oxidative stress using the real-time polymerase chain reaction (PCR). Materials and Methods: This is a cross-sectional study with patients under one year of age at FHCFM, Manaus, Amazonas, conducted from August 2021 to August 2023. Clinical data were obtained through medical records. Genomic DNA extraction was performed using the QIAamp DNA kit (Qiagen), followed by MLPA using the MRC-Holland MLPA® system with CHD-specific kits. A total of 23 SNVs related to inflammatory, thrombotic, and oxidative stress factors were analyzed using TaqMan assays in qPCR. Results: Were characterized 19 CHD phenotypes, with a higher prevalence of complex CHD cases. Were documented 12 fatalities, with high levels of urea, creatinine, AST, ALT, CRP, GGT, NT-proBNP and acidosis (p<0.001). Discussion: Our findings suggest a close relationship between CHD and a systemic impact with chronic/acute kidney failure and hepatopathies. The prevalence distribution at FHCFM aligns with the literature, although rare cases and deaths associated with inflammation, renal, and hepatic failure were recorded—severe systemic impacts requiring sequential surgeries and individualized approaches. The literature supports the high incidence of genetic alterations in CHD patients, suggesting that these variants, with hemodynamic and inflammatory impacts, are fundamental for improving the understanding of CHD genesis and identifying biomarkers for early diagnosis and clinical prognosis. Conclusion: There is a lack of data on CHD in Amazonas. Laboratory analyses revealed no significant differences between male and female CHD patients; however, in fatal cases, elevated inflammatory, renal, and hepatic markers were observed compared to survivors. The findings highlight the need for further studies and investment in biomarker research to enhance patient care and advance understanding of CHD genesis and phenotypic differences.