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Abstract
Aim: FAAH is a membrane enzyme that terminates the activity of a large class of endogenous signaling lipids. Recent studies suggest that the FAAH Pro129Thr polymorphism is a common mutation in the FAAH gene that is significantly associated with drug-addictive traits. This study investigated the association of the Pro129Thr polymorphism of the FAAH gene with methamphetamine dependence, methamphetamine-induced psychosis, manic episodes and panic disorder in a Malaysian population. Materials & methods: This polymorphism was genotyped in 232 male methamphetamine-dependent subjects and in 241 male controls of four different ethnicities: Malay, Chinese, Kadazan–Dusun and Bajau. Intergroup statistical analyses were performed by using the χ2-square test and Fisher‘s exact test, where necessary. In cases of multiple comparisons, the Bonferroni correction was performed. Results: Our results indicated that the FAAH Pro129Thr polymorphism showed a significant association with risk of methamphetamine dependence in the pooled subjects (odds ratio [OR]: 2.017; p < 0.001) and in the Malay (OR: 2.829; p < 0.001) and Chinese (OR: 3.685; p < 0.001) groups. We also found an association of this polymorphism with episodes of methamphetamine-induced mania in the Malay group (OR: 2.836; p = 0.035). However, there was no association between this polymorphism and age of onset of drug use or the occurrence of methamphetamine-induced psychosis or of panic disorder. Conclusion: Our findings suggest that the FAAH Pro129Thr polymorphism may contribute to methamphetamine dependence in the Malay and Chinese ethnic groups.
Original submitted 4 October 2012; Revision submitted 1 February 2013
Acknowledgements
The authors thank the Papar Rehabilitation Centre, Sabah, for their collaboration and permission to obtain samples from drug addicts; the Luyang Health Clinic, Kota Kinabalu, Sabah, for their permission to obtain samples from healthy controls; AR Rusdi from the Department of Psychological Medicine; and C Devika and DA Yamunah from the Department of Pharmacology, Faculty of Medicine, University of Malaya, who assisted with sample collection and interviews of the subjects of the study.
Disclaimer
The University of Malaya had no role in study design; in the collection, analysis and interpretation of the data; in the writing of the report; or in the decision to submit the paper for publication.
Financial & competing interests disclosure
This work was supported by Research University Grant FS151/2007C and RG443-12HTM from the University of Malaya and high impact research (HIR) Ministry of Higher Education (MOHE) Grant H000025-20001. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Ethical conduct of research
The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.