Research Article
Volume 10 Issue 8 - 2022
Genotype Analysis of Single Nucleotide Variant in NCF4 and CBR3 Genes Associated with Reduced Systolic Fractional Shortening in Pediatric Patients with Acute Lymphoblastic Leukemia Treated with Doxorubicin
Jesús Alonso Gándara-Mireles1,2, Ismael Lares-Asseff1,2*, Elio Aarón Reyes Espinoza3, Javier G Blanco5, Antonio Emilio González Font4, Lourdes Patricia Córdova Hurtado3, Verónica Loera-Castañeda1,2, Ignacio Villanueva Fierro1,2, Isaías Chairez Hernández1, Hugo Payan-Gándara3, Leslie Patrón Romero6 and Horacio Reyes-Almanza6
1Academia de Genómica, Instituto Politécnico Nacional, CIIDIR-Unidad Durango, México
2Red Latinoamericana de Implementación y Validación de Guías Clínicas Farmacogenómicas (RELIVAF-CYTED)
3Servicio de Hemato-Oncología Pediátrica, Centro Estatal de Cancerología, CECAN Durango, México
4Servicio de Cardiología Pediátrica, Hospital Materno Infantil, Servicios de Salud de Durango, México; México
5School of Pharmacy and Pharmaceutical Sciences, University of Buffalo, The State University of New York
6Facultad de Medicina y Psicología de la Universidad Autónoma de Baja California, Tijuana, México
*Corresponding Author: Ismael Lares-Asseff, Academia de Genómica, Instituto Politécnico Nacional, CIIDIR-Unidad Durango, México.
Received: June 20, 2022; Published: July 27, 2022


Cardiotoxicity (CT) is a frequent complication due to the use of anthracyclines (AC) in chemotherapy in various types of cancer. The reduction in the systolic shortening fraction (SF) is an echocardiographic parameter that, together with other biochemical values, is used to assess the presence of CT. Studies suggest that some genetic variants may be involved in the risk of cardiotoxicity due to the use of anthracyclines. Although it has been reported that SF alone cannot be taken as a measurement to definitely assess CT due to the use of AC, reports documenting the impact of single nucleotide variant (SNV) on CT risk considering SF as a marker in pediatric patients from Latin American countries with cancer, are scarce. This study aimed to evaluate the association between the genotypic status of NCF4 rs1883112 and CBR3 rs1056892 SNV with the SF indicative of CT by AC in a group of Mexican children with acute lymphoblastic leukemia (ALL). Sixty-nine children (6 to 17 years of age) with ALL were treated at the Centro Estatal de Cancerología (CECAN) in Durango-Mexico. The NCF4 and CBR3 genotypes were examined by real-time PCR. Fractional shortening was evaluated as a marker of systolic CT due to the use of AC. The homozygous AA genotype of the NCF4 rs1883112 SNV was significantly associated with reduced SF by the use of AC (OR = 8.87, 95% CI = 1.8066 to 147.6678, p = 0.01). There was a significant association between the dominant homozygous GG genotype of the CBR3 rs1056892 SNV and the reduced SF by the use of AC (OR = 5.33, 95% CI = 1.4008 to 20.3060, p = 0.01). This pilot study suggests that selected SNV may affect the risk of CT by AC, SF may be a value that, together with other parameters such as left ventricular ejection fraction (LVEF) and diastolic filling volume may give a broader picture of CT risk in Mexican pediatric patients treated with AC.

Keywords: Fractional shortening; Cardiotoxicity; Anthracyclines; Leukemia


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Citation: Ismael Lares-Asseff., et al. “Genotype Analysis of Single Nucleotide Variant in NCF4 and CBR3 Genes Associated with Reduced Systolic Fractional Shortening in Pediatric Patients with Acute Lymphoblastic Leukemia Treated with Doxorubicin”. EC Pharmacology and Toxicology 10.8 (2022): 14-25.

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