A missense mutation in human fatty acid amide hydrolase associated with problem drug use
Year: 2002
Type: article
Study design: Observational Study
Abstract: Problem drug use and dependence are neurobehavioral disorders of complex origin. Although environmental factors contribute to drug abuse and addiction, genetic factors also play a significant role estimated at 40-60% of the total risk. Nonetheless, the precise identities of human genes that confer vulnerability to problem drug use remain mostly unknown. Here, we describe a natural single nucleotide polymorphism in the human gene that encodes the principal endocannabinoid-inactivating enzyme, fatty acid amide hydrolase (FAAH), that in homozygous form is strongly associated with both street drug use and problem drug/alcohol use. This single nucleotide polymorphism results in a missense mutation (385C-->A) that converts a conserved proline residue to threonine (Pro129-->Thr), producing a FAAH variant that displays normal catalytic properties but an enhanced sensitivity to proteolytic degradation. Collectively, these results suggest that genetic mutations in FAAH may constitute important risk factors for problem drug use and support a potential link between functional abnormalities in the endogenous cannabinoid system and drug abuse and dependence.
Authors: Jack C. Sipe, Kyle Chiang, Alexandra L. Gerber, Ernest Beutler, Benjamin F. Cravatt
Institution: Scripps Research Institute
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2054936982