Terapia anticoagulante : efecto de los polimorfismos de los genes CALU, ApoE y factores demográficos y clínicos en la farmacoterapia con anti-vitamínicos K
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Fecha
2024
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Idioma
es
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Universidad Andrés Bello
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Licencia CC
Licencia CC
Resumen
La fibrilación auricular (FA), es la contracción anormal de las aurículas del corazón, que puede
conllevar complicaciones tromboembólicas y se trata principalmente con anticoagulantes orales, como el
acenocumarol. Debido a su estrecho margen terapéutico, es esencial ajustar cuidadosamente la dosis de este
medicamento, considerando la variabilidad individual influenciada por factores genéticos, como los
polimorfismos en los genes CALU y ApoE, así como por el estilo de vida.
El gen CALU, involucrado en la homeostasis del calcio y el metabolismo hepático, presenta
polimorfismos (rs339097, rs2290228, rs1043550) que se han relacionado con mayores dosis requeridas de
warfarina, lo que sugiere una influencia similar en la dosis de acenocumarol. Por otro lado, la enzima ApoE,
definida por tres alelos (ε2, ε3 y ε4), también influye en la respuesta a la terapia anticoagulante.
Este estudio tuvo como objetivo determinar el perfil genotípico de los polimorfismos en ApoE
(rs429358, rs7412) y CALU (rs1043550) en pacientes con FA bajo terapia con acenocumarol, evaluando su
relación con factores clínicos como el consumo de tabaco y aguas de hierbas. Se reclutaron 174 pacientes de
dos hospitales chilenos, y se realizó la genotipificación mediante PCR en tiempo real.
Los resultados mostraron tendencias, aunque no siempre significativas, en la asociación del
polimorfismo CALU (rs1043550) con la coagulación y la dosificación de acenocumarol. El genotipo G/G del
polimorfismo CALU se asoció con un mayor requerimiento de dosis. En cuanto a ApoE, no se encontraron
asociaciones significativas con la dosis de acenocumarol, aunque el genotipo ε2/ε3 requería dosis mayores.
El estudio destaca la complejidad de la respuesta al acenocumarol, influenciada por los
polimorfismos en CALU y ApoE, así como por factores clínicos y demográficos, sugiriendo la necesidad de
investigaciones adicionales para optimizar la dosificación mediante enfoques personalizados.
Atrial fibrillation (AF) is the abnormal contraction of the atria of the heart, which can lead to thromboembolic complications and is primarily treated with oral anticoagulants, such as acenocoumarol. Due to its narrow therapeutic window, precise dosing of acenocoumarol is essential, considering individual variability influenced by genetic factors, such as polymorphisms in the CALU and ApoE genes, as well as lifestyle factors. The CALU gene, involved in calcium homeostasis and hepatic metabolism, has polymorphisms (rs339097, rs2290228, rs1043550) associated with higher warfarin dose requirements, suggesting a similar influence on acenocoumarol dosing. On the other hand, the ApoE enzyme, defined by three alleles (ε2, ε3, and ε4), also affects the response to anticoagulant therapy. This study aimed to determine the genotypic profile of polymorphisms in ApoE (rs429358, rs7412) and CALU (rs1043550) in AF patients under acenocoumarol therapy, evaluating their relationship with clinical factors such as smoking and herbal tea consumption. A total of 174 patients from two Chilean hospitals were recruited, and genotyping was performed using real-time PCR. The results showed trends, though not always significant, in the association of the CALU (rs1043550) polymorphism with coagulation and acenocoumarol dosing. The G/G genotype of the CALU polymorphism was associated with higher dose requirements. Regarding ApoE, no significant associations were found with acenocoumarol dosing, although the ε2/ε3 genotype required higher doses. The study highlights the complexity of the response to acenocoumarol, influenced by polymorphisms in CALU and ApoE, as well as by clinical and demographic factors, suggesting the need for further research to optimize dosing through personalized approaches.
Atrial fibrillation (AF) is the abnormal contraction of the atria of the heart, which can lead to thromboembolic complications and is primarily treated with oral anticoagulants, such as acenocoumarol. Due to its narrow therapeutic window, precise dosing of acenocoumarol is essential, considering individual variability influenced by genetic factors, such as polymorphisms in the CALU and ApoE genes, as well as lifestyle factors. The CALU gene, involved in calcium homeostasis and hepatic metabolism, has polymorphisms (rs339097, rs2290228, rs1043550) associated with higher warfarin dose requirements, suggesting a similar influence on acenocoumarol dosing. On the other hand, the ApoE enzyme, defined by three alleles (ε2, ε3, and ε4), also affects the response to anticoagulant therapy. This study aimed to determine the genotypic profile of polymorphisms in ApoE (rs429358, rs7412) and CALU (rs1043550) in AF patients under acenocoumarol therapy, evaluating their relationship with clinical factors such as smoking and herbal tea consumption. A total of 174 patients from two Chilean hospitals were recruited, and genotyping was performed using real-time PCR. The results showed trends, though not always significant, in the association of the CALU (rs1043550) polymorphism with coagulation and acenocoumarol dosing. The G/G genotype of the CALU polymorphism was associated with higher dose requirements. Regarding ApoE, no significant associations were found with acenocoumarol dosing, although the ε2/ε3 genotype required higher doses. The study highlights the complexity of the response to acenocoumarol, influenced by polymorphisms in CALU and ApoE, as well as by clinical and demographic factors, suggesting the need for further research to optimize dosing through personalized approaches.
Notas
Memoria (Ingeniera en Biotecnología)
Este trabajo fue financiado por el Proyecto FONDEF IT20I003 – ANID.
Este trabajo fue financiado por el Proyecto FONDEF IT20I003 – ANID.
Palabras clave
Anticoagulantes, Investigaciones, Polimorfismo Genético