Research Article

Relevance of NR1I2 variants on carbamazepine therapy in Mexican Mestizos with epilepsy at a tertiary-care hospital

Metropolitan Autonomous University, Campus Xochimilco, Calzada del Hueso 1100, Villa Quietud, 04960, Coyoacán, Mexico City, Mexico

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Helgi Jung-Cook

https://orcid.org/0000-0002-2032-4753

National Institute of Neurology & Neurosurgery, Manuel Velasco Suárez, Insurgentes Sur 3877, La Fama, 14269, Tlalpan, Mexico City, Mexico

National Autonomous University of Mexico, Mexico City, Mexico, Av. Universidad 3000, C.U., 04510, Coyoacán, Mexico City, Mexico

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Iris E Martínez-Juárez

https://orcid.org/0000-0001-6512-5312

National Institute of Neurology & Neurosurgery, Manuel Velasco Suárez, Insurgentes Sur 3877, La Fama, 14269, Tlalpan, Mexico City, Mexico

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Nancy Monroy-Jaramillo

https://orcid.org/0000-0003-2611-0972

National Institute of Neurology & Neurosurgery, Manuel Velasco Suárez, Insurgentes Sur 3877, La Fama, 14269, Tlalpan, Mexico City, Mexico

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Alberto Ortega-Vázquez

https://orcid.org/0000-0003-2803-9444

Metropolitan Autonomous University, Campus Xochimilco, Calzada del Hueso 1100, Villa Quietud, 04960, Coyoacán, Mexico City, Mexico

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Irma S Rojas-Tomé

National Institute of Neurology & Neurosurgery, Manuel Velasco Suárez, Insurgentes Sur 3877, La Fama, 14269, Tlalpan, Mexico City, Mexico

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Pedro Dorado

https://orcid.org/0000-0003-4100-721X

Biosanitary Research Institute, INUBE Extremadura University, Avda. de Elvas, Badajoz, 06006, Spain

Department of Medical-Surgery Therapeutics, University of Extremadura, Avda. Virgen del Puerto, Plasencia, 10600, Spain

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Eva Peñas-Lledó

https://orcid.org/0000-0001-9478-3445

Biosanitary Research Institute, INUBE Extremadura University, Avda. de Elvas, Badajoz, 06006, Spain

Faculty of Medicine, University of Extremadura, Av. de Elvas, s/n, Badajoz, 06006, Spain

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Adrián Llerena

https://orcid.org/0000-0002-5663-7081

Biosanitary Research Institute, INUBE Extremadura University, Avda. de Elvas, Badajoz, 06006, Spain

Faculty of Medicine, University of Extremadura, Av. de Elvas, s/n, Badajoz, 06006, Spain

CICAB Clinical Research Center, Extremadura University Hospital, Campus Universitario, Av. de Elvas, s/n, Badajoz, 06080, Spain

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Marisol López-López

*Author for correspondence: Tel.: +52 55 5483 7250;

E-mail Address: marisollopezlopez@gmail.com

https://orcid.org/0000-0002-3954-8052

Metropolitan Autonomous University, Campus Xochimilco, Calzada del Hueso 1100, Villa Quietud, 04960, Coyoacán, Mexico City, Mexico

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Published Online:6 Oct 2021https://doi.org/10.2217/pgs-2021-0081

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Abstract

Aim: We evaluated the potential influence of genetic (CYP3A5, EPHX1, NR1I2, HNF4A, ABCC2, RALBP1, SCN1A, SCN2A and GABRA1) and nongenetic factors on carbamazepine (CBZ) response, adverse drug reactions and CBZ plasma concentrations in 126 Mexican Mestizos (MM) with epilepsy. Subjects & methods: Patients were genotyped for 27 variants using TaqMan^® assays. Results: CBZ response was associated with NR1I2 variants and lamotrigine cotreatment. CBZ-induced adverse drug reactions were related to antiepileptic polytherapy and SCN1A rs2298771/rs3812718 haplotype. CBZ plasma concentrations were influenced by NR1I2-rs2276707 and -rs3814058, and by phenytoin cotreatment. CBZ daily dose was also influenced by NR1I2-rs3814055 and EPHX1-rs1051740. Conclusion: Interindividual variability in CBZ treatment was partly explained by NR1I2, EPHX1 and SCN1A variants, as well as antiepileptic cotreatment in MM with epilepsy.

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 22, No. 15

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Received 23 June 2021

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To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/pgs-2021-0081

Author contributions

I Fricke-Galindo was responsible for the design of the work, acquisition, analysis, interpretation of data, drafting the work and final approval of the version. H Jung-Cook contributed to the design of the work, interpretation of data, revising the work critically for important intellectual content and final approval of the version. IE Martínez-Juárez was responsible for the interpretation of data, revising the work critically for important intellectual content and final approval of the version. N Monroy-Jaramillo contributed to the conception of the work, analysis and interpretation of data, revising the work critically for important intellectual content and final approval of the version. A Ortega-Vázquez was responsible for the acquisition of data, revising the work critically for important intellectual content and final approval of the version. IS Rojas-Tomé contributed to the analysis of data, revising the work critically for important intellectual content and final approval of the version. P Dorado was responsible for the analysis and interpretation of data, revising the work critically for important intellectual content and final approval of the version. E Peñas-Lledó contributed to the conception of the work, revising the work critically for important intellectual content and final approval of the version. A Llerena was responsible for the design of the work, revising the work critically for important intellectual content and final approval of the version. M López-López contributed to the design of the work, revising the work critically for important intellectual content and final approval of the version. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Financial & competing interests disclosure

The authors are grateful for support from the Consejo Nacional de Ciencia y Tecnología (CONACYT) of Mexico (grant no. 167261). 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 they have obtained appropriate institutional review board approval (protocol [#41/12] approved by the INNNMVS Research and Ethics Review Board) and have followed the principles outlined in the Declaration of Helsinki for human investigations. In addition, informed consent has been obtained from the participants involved.

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