ALDH5A1 variability in opioid dependent patients could influence response to methadone treatment

作者：Fonseca Francina; Gratacos Monica; Escaramis Georgia; De Cid Rafael; Martin Santos Rocio; Farre Magi; Estivill Xavier; Torrens Marta^*

来源：European Neuropsychopharmacology, 2014, 24(3): 420-424.

DOI：10.1016/j.euroneuro.2013.10.003

• ALDH5A1 gene
• Gamma-aminobutyric acid
• Gamma-hydroxibutyric acid
• (GHB)
• Methadone maintenance treatment (MMT)
• Opioid dependence
• Pharmacogenetics

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% Cl [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.

• 出版日期2014-3