title: Nerve growth factor β polypeptide (NGFB) genetic variability: association with the methadone dose required for effective maintenance treatment.
abstract: Opioid addiction is a chronic disease with high genetic contribution and a large inter-individual variability in therapeutic response. The goal of this study was to identify pharmacodynamic factors that modulate methadone dose requirement. The neurotrophin family is involved in neural plasticity, learning, memory and behavior and deregulated neural plasticity may underlie the pathophysiology of drug addiction. Brain-derived neurotrophic factor (BDNF) was shown to affect the response to methadone maintenance treatment. This study explores the effects of polymorphisms in the nerve growth factor (β polypeptide) gene, NGFB, on the methadone doses required for successful maintenance treatment for heroin addiction. Genotypes of 14 NGFB polymorphisms were analyzed for association with the stabilizing methadone dose in 72 former severe heroin addicts with no major co-medications. There was significant difference in methadone doses required by subjects with different genotypes of the NGFB intronic single-nucleotide polymorphism rs2239622 (P=0.0002). These results may have clinical importance.
authors.affiliation: Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY 10065, USA. levrano@rockefeller.edu
authors.forename: O
authors.initials: O
authors.lastname: Levran
authors.forename: E
authors.initials: E
authors.lastname: Peles
authors.forename: S
authors.initials: S
authors.lastname: Hamon
authors.forename: M
authors.initials: M
authors.lastname: Randesi
authors.forename: C
authors.initials: C
authors.lastname: Zhao
authors.forename: B
authors.initials: B
authors.lastname: Zhang
authors.forename: M
authors.initials: M
authors.lastname: Adelson
authors.forename: M J
authors.initials: MJ
authors.lastname: Kreek
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006556:Heroin Dependence / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008691:Methadone / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: C502240:NGF protein, human; D020932:Nerve Growth Factor; D008691:Methadone