The genetic basis of the endocannabinoid system and drug addiction in humans

被引:47
作者
Antonio Lopez-Moreno, Jose [1 ]
Echeverry-Alzate, Victor [1 ]
Buehler, Kora-Mareen [1 ]
机构
[1] Univ Complutense, Lab Psicobiol, Dept Psychobiol, Fac Psychol, E-28223 Madrid, Spain
关键词
Cannabinoid; CNR1; drug addiction; FAAH; genetic polymorphism; human; SNP; CANNABINOID RECEPTOR GENE; ACID-AMIDE-HYDROLASE; DEPENDENCE SYMPTOMS; MISSENSE MUTATION; OPIOID SYSTEMS; (AAT)N REPEAT; BRAIN REWARD; CNR1; GENE; ASSOCIATION; ALCOHOL;
D O I
10.1177/0269881111416689
中图分类号
R74 [神经病学与精神病学];
学科分类号
100204 [神经病学];
摘要
The cannabinoid receptor (CNR1) and the fatty acid amide hydrolase (FAAH) genes are located on chromosomes 6 and 1 in the 6q15 and 1p33 cytogenetic bands, respectively. CNR1 encodes a seven-transmembrane domain protein of 472 amino acids, whereas FAAH encodes one transmembrane domain of 579 amino acids. Several mutations found in these genes lead to altered mRNA stability and transcription rate or a reduction of the activity of the encoded protein. Increasing evidence shows that these functional mutations are related to dependence upon cocaine, alcohol, marijuana, heroin, nicotine and other drugs. One of the most compelling associations is with the C385A single nucleotide polymorphism (SNP), which is found in the FAAH gene. For all of the genetic polymorphisms reviewed here, it is difficult to form overall conclusions due to the high diversity of population samples being studied, ethnicity, the use of volunteers, heterogeneity of the recruitment criteria and the drug addiction phenotype studied. Care should be taken when generalizing the results from different studies. However, many works have repeatedly associated polymorphisms in the CNR1 and FAAH genes with drug-related behaviours; this suggests that these genes should be examined in further genetic studies focusing on drug addiction and other psychiatric disorders.
引用
收藏
页码:133 / 143
页数:11
相关论文
共 70 条
[1]
Evidence for Association Between Polymorphisms in the Cannabinoid Receptor 1 (CNR1) Gene and Cannabis Dependence [J].
Agrawal, Arpana ;
Wetherill, Leah ;
Dick, Danielle M. ;
Xuei, Xiaoling ;
Hinrichs, Anthony ;
Hesselbrock, Victor ;
Kramer, John ;
Nurnberger, John I., Jr. ;
Schuckit, Marc ;
Bierut, Laura J. ;
Edenberg, Howard J. ;
Foroud, Tatiana .
AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS, 2009, 150B (05) :736-740
[2]
The effects of cannabinoids on the brain [J].
Ameri, A .
PROGRESS IN NEUROBIOLOGY, 1999, 58 (04) :315-348
[3]
The role of endocannabinoid transmission in cocaine addiction [J].
Arnold, JC .
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 2005, 81 (02) :396-406
[4]
(AAT)n repeat in the cannabinoid receptor gene (CNR1):: association with cocaine addiction in an African-Caribbean population [J].
Ballon, N ;
Leroy, S ;
Roy, C ;
Bourdel, MC ;
Charles-Nicolas, A ;
Krebs, MO ;
Poirier, MF .
PHARMACOGENOMICS JOURNAL, 2006, 6 (02) :126-130
[5]
Depression in Parkinson's disease is related to a genetic polymorphism of the cannabinoid receptor gene (CNR1) [J].
Barrero, FJ ;
Ampuero, I ;
Morales, B ;
Vives, F ;
del Castillo, JDL ;
Hoenicka, J ;
Yébenes, JG .
PHARMACOGENOMICS JOURNAL, 2005, 5 (02) :135-141
[6]
Critical enzymes involved in endocannabinoid metabolism [J].
Basavarajappa, Balapal S. .
PROTEIN AND PEPTIDE LETTERS, 2007, 14 (03) :237-246
[7]
Methodological Issues in Molecular Genetic Studies of Mental Disorders [J].
Bearden, Carrie E. ;
Jasinska, Anna J. ;
Freimer, Nelson B. .
ANNUAL REVIEW OF CLINICAL PSYCHOLOGY, 2009, 5 :49-69
[8]
CNR1 gene polymorphisms in addictive disorders: a systematic review and a meta-analysis [J].
Benyamina, Amine ;
Kebir, Oussama ;
Blecha, Lisa ;
Reynaud, Michel ;
Krebs, Marie-Odile .
ADDICTION BIOLOGY, 2011, 16 (01) :1-6
[9]
Functionally selective cannabinoid receptor signalling: Therapeutic implications and opportunities [J].
Bosier, Barbara ;
Muccioli, Giulio G. ;
Hermans, Emmanuel ;
Lambert, Didier M. .
BIOCHEMICAL PHARMACOLOGY, 2010, 80 (01) :1-12
[10]
Cannabinoid receptor 1 gene association with nicotine dependence [J].
Chen, Xiangning ;
Williamson, Vernell S. ;
An, Seon-Sook ;
Hettema, John M. ;
Aggen, Steven H. ;
Neale, Michael C. ;
Kendler, Kenneth S. .
ARCHIVES OF GENERAL PSYCHIATRY, 2008, 65 (07) :816-824