TY - JOUR
T1 - CES1 and SLC6A2 Genetic Variants As Predictors of Response To Methylphenidate in Autism Spectrum Disorders
AU - Hernandez, Marta H.
AU - Bote, Valentin
AU - Serra-Llovich, Alexandre
AU - Cendros, Marc
AU - Salazar, Juliana
AU - Mestres, Conxita
AU - Guijarro, Silvina
AU - Alvarez, Aida
AU - Lamborena, Cristina
AU - Mendez, Iria
AU - Sanchez, Bernardo
AU - Hervas, Amaia
AU - Arranz, Maria J.
N1 - Funding Information:
This project was supported by grants from Secretaria de Recerca i Universitats de la Generalitat de Catalunya i la Universitat Ramon Llull (2021-URL-Proj-002) and by a grant from the Institute of Health Carlos III (FIS PI21/01946).
Publisher Copyright:
© 2022 Hernandez et al.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - ADHD
KW - ASD
KW - CES1
KW - SLC6A2
KW - Attention deficit hyperactivity disorders
KW - Autistic spectrum disorders
KW - Methylphenidate
UR - http://www.scopus.com/inward/record.url?scp=85141400971&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=pure_univeritat_ramon_llull&SrcAuth=WosAPI&KeyUT=WOS:000883720300001&DestLinkType=FullRecord&DestApp=WOS
U2 - 10.2147/PGPM.S377210
DO - 10.2147/PGPM.S377210
M3 - Article
AN - SCOPUS:85141400971
SN - 1178-7066
VL - 15
SP - 951
EP - 957
JO - Pharmacogenomics and Personalized Medicine
JF - Pharmacogenomics and Personalized Medicine
ER -