CES1 and SLC6A2 Genetic Variants As Predictors of Response To Methylphenidate in Autism Spectrum Disorders
Hernández Hernández, Marta (Facultat de Ciències de la Salut Blanquerna)
Bote, Valentin (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Serra-Llovich, Alexandre (Fundació Docència i Recerca Mútua Terrassa. Unitat del Laboratori de Recerca)
Cendros, Marc (EUGENOMIC Genómica y Farmacogenética)
Salazar, Juliana (Institut d'Investigació Biomèdica Sant Pau)
Mestres, Concepció (Facultat de Ciències de la Salut Blanquerna)
Guijarro, Silvina (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Àlvarez, Aida (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Lamborena, Cristina (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Mendez, Iria (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Sanchez, Bernardo (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Hervas, Amaia (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Arranz, María Jesús (Facultat de Ciències de la Salut Blanquerna)

Date:	2022
Abstract:	Purpose: Autistic spectrum disorders (ASD) children and adolescents usually present comorbidities, with 40-70% of them affected by attention deficit hyperactivity disorders (ADHD). The first option of pharmacological treatment for these patients is methylphe-nidate (MPH). ASD children present more side effects and poorer responses to MPH than ADHD children. The objective of our study is to identify genetic biomarkers of response to MPH in ASD children and adolescents to improve its efficacy and safety. Patients and Methods: A retrospective study with a total of 140 ASD children and adolescents on MPH treatment was included. Fifteen polymorphisms within genes coding for the MPH target NET1 (SLC6A2) and for its primary metabolic pathway (CES1) were genotyped. Multivariate analyses including response phenotypes (efficacy, side-effects, presence of somnolence, irritability, mood alterations, aggressivity, shutdown, other side-effects) were performed for every polymorphism and haplotype. Results: Single marker analyses considering gender, age, and dose as covariates showed association between CES1 variants and MPH-induced side effects (rs2244613-G (p=0. 04), rs2302722-C (p=0. 02), rs2307235-A (p=0. 03), and rs8192950-T alleles (p=0. 03)), and marginal association between the CES1 rs2302722-C allele and presence of somnolence (p=0. 05) and the SLC6A2 rs36029-G allele and shutdown (p=0. 05). A CES1 haplotype combination was associated with efficacy and side effects (p=0. 02 and 0. 03 respectively). SLC6A2 haplotype combination was associated with somnolence (p=0. 05). Conclusion: CES1 genetic variants may influence the clinical outcome of MPH treatment in ASD comorbid with ADHD children and adolescents.
Grants:	Agència de Gestió d'Ajuts Universitaris i de Recerca 2021-URL-Proj-002 Instituto de Salud Carlos III FIS PI21/01946
Note:	Altres ajuts: Secretaria de Recerca i Universitats de la Generalitat de Catalunya i Universitat Ramon Llull (2021-URL-Proj-002).
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	CES1 ; SLC6A2 ; Autistic spectrum disorders ; ASD ; Methylphenidate ; Attention deficit hyperactivity disorders ; ADHD
Published in:	Pharmacogenomics and Personalized Medicine, Vol. 15 (2022) , p. 951-957, ISSN 1178-7066

DOI: 10.2147/PGPM.S377210
PMID: 36393977

7 p, 559.9 KB

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