African-specific variability in the acetylcholine muscarinic receptor M4: association with cocaine and heroin addiction.
This study was designed to determine whether polymorphisms in acetylcholine receptors contribute to opioid dependence and/or cocaine dependence.



The sample (n = 1860) was divided by drug and ancestry, and 55 polymorphisms (nine genes) were analyzed.



Of the 20 SNPs that showed nominally significant associations, the association of the African-specific CHRM4 SNP rs2229163 (Asn417=) with cocaine dependence survived correction for multiple testing (Pcorrected = 0.047). CHRM4 is located in a region of strong linkage disequilibrium on chromosome 11 that includes genes associated with schizophrenia. CHRM4 SNP rs2229163 is in strong linkage disequilibrium with several African-specific SNPs in DGKZ and AMBRA1.



Cholinergic receptors' variants may contribute to drug addiction and have a potential role as pharmacogenetic markers.
The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY 10065, USA.
Orna
O
Levran
The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY 10065, USA.
Matthew
M
Randesi
Dr Miriam & Sheldon G Adelson Clinic for Drug Abuse Treatment & Research, Tel Aviv Elias Sourasky Medical Center, Tel Aviv, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Einat
E
Peles
Center for Clinical & Translational Science, The Rockefeller University, New York, NY 10065, USA.
Joel
J
Correa da Rosa
Institute of Psychology, Chinese Academy of Sciences, Beijing, China.|The Laboratory of Statistical Genetics, The Rockefeller University, New York, NY 10065, USA.
Jurg
J
Ott
VA New York Harbor Healthcare System & NYU School of Medicine, New York, NY 10016, USA.
John
J
Rotrosen
The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY 10065, USA.|Dr Miriam & Sheldon G Adelson Clinic for Drug Abuse Treatment & Research, Tel Aviv Elias Sourasky Medical Center, Tel Aviv, Israel.|Dr Miriam & Sheldon G Adelson Clinic for Drug Abuse Treatment & Research, Las Vegas, NV 89169, USA.
Miriam
M
Adelson
The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY 10065, USA.
Mary Jeanne
MJ
Kreek
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D044383:Black People / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D019970:Cocaine-Related Disorders / Q000235:genetics*; D019852:Diacylglycerol Kinase / Q000235:genetics; D014644:Genetic Variation; D006556:Heroin Dependence / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D011110:Polymorphism, Genetic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D043588:Receptor, Muscarinic M4; D011976:Receptors, Muscarinic / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics; D044465:White People / Q000235:genetics
C553334:AMBRA1 protein, human; D048868:Adaptor Proteins, Signal Transducing; C000597933:CHRM4 protein, human; D043588:Receptor, Muscarinic M4; D011976:Receptors, Muscarinic; C526463:DGKZ protein, human; D019852:Diacylglycerol Kinase
African ancestry; CHRM4; cholinergic receptors; cocaine addiction; opioid addiction