ALDH5A1 variability in opioid dependent patients could influence response to methadone treatment.
Methadone maintenance treatment is the most widely-used therapy in opioid dependence, but some patients relapse or drop out from treatment. We genotyped a genetic variant in the succinic semialdehyde dehydrogenase enzyme gene, ALDH5A1, and found that subjects carrying the T variant allele have a higher risk to be nonresponders to methadone treatment (OR=3.16; 95% CI [1.48-6.73], P=0.0024). This could be due to a reduction in the ALDH5A1 enzyme activity, that would increase endogenous gamma-hydroxbutyric acid (GHB) and gamma-aminobutyric acid (GABA) levels and therefore, inducing symptoms such as sedation and impaired pschomotor performance. These neuropsychological effects related with the reduction in enzyme activity could be responsible for a higher propensity to relapse in these genetically predisposed patients.
Institut de Neuropsiquiatria i Addicions, Hospital del Mar, Barcelona, Spain; Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain.
Francina
F
Fonseca
CIBER Epidemiología y Salud Pública (CIBERESP) and Genes and Disease Program, Barcelona, Spain.
Mònica
M
Gratacòs
CIBER Epidemiología y Salud Pública (CIBERESP) and Genes and Disease Program, Barcelona, Spain.
Geòrgia
G
Escaramís
CIBER Epidemiología y Salud Pública (CIBERESP) and Genes and Disease Program, Barcelona, Spain; Center for Genomic Regulation (CRG-UPF), Parc de Recerca Biomèdica (PRBB), Barcelona, Spain.
Rafael
R
De Cid
Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain; Service of Psychiatry and Psychology, Neuroscience Institute, Hospital Clinic, Institut d'Investigació Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red en Salud Mental (CIBERSAM), Barcelona, Spain; Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain.
Rocío
R
Martín-Santos
Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain; Psychiatry and Pharmacology Departments, Autonomous University of Barcelona, Barcelona, Spain.
Magi
M
Farré
CIBER Epidemiología y Salud Pública (CIBERESP) and Genes and Disease Program, Barcelona, Spain; Center for Genomic Regulation (CRG-UPF), Parc de Recerca Biomèdica (PRBB), Barcelona, Spain; Experimental and Health Sciences Department, Pompeu Fabra University, Barcelona, Spain.
Xavier
X
Estivill
Institut de Neuropsiquiatria i Addicions, Hospital del Mar, Barcelona, Spain; Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain; Psychiatry and Pharmacology Departments, Autonomous University of Barcelona, Barcelona, Spain. Electronic address: mtorrens@hospitaldelmar.cat.
Marta
M
Torrens
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D008691:Methadone / Q000627:therapeutic use*; D008875:Middle Aged; D009294:Narcotics / Q000627:therapeutic use*; D058850:Opiate Substitution Treatment; D009293:Opioid-Related Disorders / Q000188:drug therapy* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D050644:Succinate-Semialdehyde Dehydrogenase / Q000235:genetics*; D011795:Surveys and Questionnaires; D017211:Treatment Failure; D055815:Young Adult
D009294:Narcotics; C493643:ALDH5A1 protein, human; D050644:Succinate-Semialdehyde Dehydrogenase; D008691:Methadone
ALDH5A1 gene; Gamma-aminobutyric acid; Gamma-hydroxibutyric acid (GHB); Methadone maintenance treatment (MMT); Opioid dependence; Pharmacogenetics