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Papel modulador do gene MTHFR nos níveis de homocisteína na infeção por HPV
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Introdução: O cancro do colo do útero é a quarta causa de morte por cancro em mulheres, a nível global. A infeção por Papilomavírus Humano é a principal causa para o desenvolvimento de cancro cervical, não sendo causa suficiente. Entre outros fatores potenciadores, existe a variação genética em genes modificadores. O metabolismo da homocisteína está envolvido nos processos de síntese, reparação e metilação de ADN, que estão muitas vezes desregulados na carcinogénese. Objetivo: Estudar os níveis de homocisteína circulante na doença e na sua severidade, e compreender o papel modulador do gene MTHFR nesse fenótipo. Metodologia: Os dados laboratoriais foram disponibilizados anteriormente, estando em bases de dados. A análise estatística foi realizada através do software SPSS. Efetuou-se o teste U de Mann-Whitney para avaliar diferenças dos níveis de homocisteína entre um grupo de mulheres saudáveis e grupos com diferentes graus de lesão cervical. Fez-se ajuste à idade através do teste de Regressão Logística Binária. Para perceber a influência do genótipo do MTHFR nos níveis de homocisteína, realizou-se o teste T de Student. Resultados: Os níveis de homocisteína são inferiores em mulheres com patologia. O gene MTHFR não modula os níveis de homocisteína em mulheres infetadas com HPV. Conclusão: Os níveis de homocisteína podem alterar o desenvolvimento de lesões precursoras ou malignas do colo do útero. Dadas as limitações deste trabalho, recomenda-se a realização de mais investigações que estudem o papel da homocisteína, associado ao papel de outras variantes genéticas que participem neste metabolismo, com amostras populacionais maiores, de forma a obter uma maior qualidade de resultados.
Introduction: Cervical cancer is the fourth leading cause of cancer death in women, globally. Human papillomavirus infection is the main cause for the development of cervical cancer, although it is not sufficient on its own. Among other contributing factors, there is genetic variation in modifier genes. Folate and homocysteine metabolism is involved in DNA synthesis, repair, and methylation processes, which are often dysregulated in carcinogenesis. Objective: To study circulating homocysteine levels in the disease and its severity, and to understand the modulating role of the MTHFR gene in this phenotype. Methodology: Laboratory data was previously available in databases. Statistical analysis was conducted using SPSS software. The Mann-Whitney non-parametric U test was used to assess differences in homocysteine levels between a group of healthy women and groups with different degrees of cervical lesions. Age was adjusted using the Binary Logistic Regression test. To understand the influence of the MTHFR genotype on homocysteine levels, the Student's T-test was performed. Results: Homocysteine levels were lower in women with the condition. The MTHFR gene does not modulate homocysteine levels in HPV-infected women. Conclusion: Homocysteine levels may alter the development of precancerous or malignant lesions of the cervix. Given the limitations of this study, further research is recommended to study the role of homocysteine and folate, associated with the role of other genetic variants involved in this metabolism, with population samples containing a larger number of participants to obtain higher-quality results.
Introduction: Cervical cancer is the fourth leading cause of cancer death in women, globally. Human papillomavirus infection is the main cause for the development of cervical cancer, although it is not sufficient on its own. Among other contributing factors, there is genetic variation in modifier genes. Folate and homocysteine metabolism is involved in DNA synthesis, repair, and methylation processes, which are often dysregulated in carcinogenesis. Objective: To study circulating homocysteine levels in the disease and its severity, and to understand the modulating role of the MTHFR gene in this phenotype. Methodology: Laboratory data was previously available in databases. Statistical analysis was conducted using SPSS software. The Mann-Whitney non-parametric U test was used to assess differences in homocysteine levels between a group of healthy women and groups with different degrees of cervical lesions. Age was adjusted using the Binary Logistic Regression test. To understand the influence of the MTHFR genotype on homocysteine levels, the Student's T-test was performed. Results: Homocysteine levels were lower in women with the condition. The MTHFR gene does not modulate homocysteine levels in HPV-infected women. Conclusion: Homocysteine levels may alter the development of precancerous or malignant lesions of the cervix. Given the limitations of this study, further research is recommended to study the role of homocysteine and folate, associated with the role of other genetic variants involved in this metabolism, with population samples containing a larger number of participants to obtain higher-quality results.
Descrição
Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2024
Palavras-chave
Homocisteína MTHFR Papilomavírus humano Displasia cervical Neoplasias do colo do útero Genética