A nonsynonymous polymorphism in the human fatty acid amide hydrolase gene did not associate with either methamphetamine dependence or schizophrenia.

Abstract

Genetic contributions to the etiology of substance abuse and dependence are topics of major interest. Acute and chronic cannabis use can produce drug-induced psychosis resembling schizophrenia and worsen positive symptoms of schizophrenia. The endocannabinoid system is one of the most important neural signaling pathways implicated in substance abuse and dependence. The fatty acid amide hydrolase (FAAH) is a primary catabolic enzyme of endocannabinoids. To clarify a possible involvement of FAAH in the etiology of methamphetamine dependence/psychosis or schizophrenia, we examined the genetic association of a nonsynonymous polymorphism of the FAAH gene (Pro129Thr) by a case-control study. We found no significant association in allele and genotype frequencies of the polymorphism with either disorder. Because the Pro129Thr polymorphism reduces enzyme instability, it is unlikely that dysfunction of FAAH and enhanced endocannabinoid system induce susceptibility to either methamphetamine dependence/psychosis or schizophrenia.

• Authors: Yukitaka Morita, Hiroshi Ujike, Yuji Tanaka, Naohiko Uchida, Akira Nomura, Kyohei Ohtani, Makiko Kishimoto, Akiko Morio, Takaki Imamura, Ayumu Sakai, Toshiya Inada, Mutsuo Harano, Tokutaro Komiyama, Mitsuhiko Yamada, Yoshimoto Sekine, Nakao Iwata, Masaomi Iyo, Ichiro Sora, Norio Ozaki, Shigetoshi Kuroda
• Journal: Neuroscience letters (Neurosci Lett) Vol. 376 Issue 3 Pg. 182-7 (Mar 16 2005) ISSN: 0304-3940 [Print] Ireland
• PMID: 15721218 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cannabinoid Receptor Modulators
• Methamphetamine
• Amidohydrolases
• fatty-acid amide hydrolase

Topics

• Adult
• Age of Onset
• Amidohydrolases (genetics)
• Amino Acid Sequence (genetics)
• Amino Acid Substitution (genetics)
• Amphetamine-Related Disorders (enzymology, epidemiology, genetics)
• Cannabinoid Receptor Modulators (metabolism)
• Case-Control Studies
• DNA Mutational Analysis
• Female
• Gene Frequency (genetics)
• Genetic Predisposition to Disease (genetics)
• Genetic Testing
• Genotype
• Humans
• Japan (epidemiology)
• Male
• Methamphetamine (adverse effects)
• Middle Aged
• Mutation (genetics)
• Polymorphism, Genetic (genetics)
• Schizophrenia (enzymology, epidemiology, genetics)