Pharmacogenomic Study of Anthracycline-Induced Cardiotoxicity in Mexican Pediatric Patients

Abstract

Background: The aim of this study was to evaluate the association between well-defined genetic risk variants in SLC28A3, RARG and UGT1A6 and anthracycline-induced cardiotoxicity in Mexican pediatric patients. Methods: We tested a cohort of 79 children treated with anthracyclines for the presence of SLC28A3-rs7853758, RARG-rs2229774 and UGT1A6-rs17863783. Results: The SLC28A3-rs7853758 variant was more frequent in this cohort, while the UGT1A6-rs17863783 and RARG-rs2229774 variants were present at lower frequencies. A clinically important decrease of fractional shortening was associated with SLC28A3-rs7853758 variant. Conclusion: In this cohort, 39.2% of patients carried the protective SLC28A3 variant. A small number of tested patients have the risk variants of UGT1A6 and RARG. None of the patients shared the two risk variants.

Keywords::

• anthracycline
• cardiotoxicity
• fractional shortening
• Mexican pediatric patients
• pharmacogenomics
• RARG
• SLC28A3
• UGT1A6

Author contributions

JL Vargas-Neri, B Carleton, CJ Ross, P Clark and M Medeiros are responsible for the conception and design of the study. JL Vargas-Neri, P Clark, B Carleton and G Castañeda-Hernández were responsible for data acquisition and data validation. JL Vargas-Neri, B Carleton, CJ Ross and P Clark were responsible for data analysis and interpretation. All authors were responsible for overall content, manuscript writing and final approval of the manuscript.

Acknowledgments

The authors are thankful to all patients and families that participated in this study; they also want to acknowledge the support of the follow contributors: N Balderrábano-Saucedo, M Palomo-Colli, D Castelán-Martínez, M de Jesús Estrada, E López-Aguilar, R Rivas-Ruiz and F Rodríguez-Islas. The authors also acknowledge the support of the Canadian Pharmacogenomic Network for Drug Safety Consortium. Also to the Consejo Nacional de Ciencia y Tecnología for the support. JL Vargas-Neri wants to thank to the Universidad Nacional Autónoma de México, program of Master’s and Doctorate in Health Sciences.

Financial & competing interests disclosure

This research was partially supported by an unrestricted grant of Scientific Institute Pfizer, Mexico. The analysis of the genetic samples was supported by the Canadian Pharmacogenomic Network for Drug Safety Consortium. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that this study was conducted according to the principles of the Declaration of Helsinki and approved by local ethics committees (registration code: HIM-2013-062 SSA 1091, IMSS: R-2013-785-040). Written informed consent or assent was obtained from all patients or their parents or legal guardians.

Additional information

Funding

This research was partially supported by an unrestricted grant of Scientific Institute Pfizer, Mexico. The analysis of the genetic samples was supported by the Canadian Pharmacogenomic Network for Drug Safety Consortium. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.