Orna Levran1, Matthew Randesi1, Einat Peles2,3, Joel Correa da Rosa4, Jurg Ott5,6, John Rotrosen7, Miriam Adelson1,2,8, Mary Jeanne Kreek1. 1. The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY 10065, USA. 2. Dr Miriam & Sheldon G Adelson Clinic for Drug Abuse Treatment & Research, Tel Aviv Elias Sourasky Medical Center, Tel Aviv, Israel. 3. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 4. Center for Clinical & Translational Science, The Rockefeller University, New York, NY 10065, USA. 5. Institute of Psychology, Chinese Academy of Sciences, Beijing, China. 6. The Laboratory of Statistical Genetics, The Rockefeller University, New York, NY 10065, USA. 7. VA New York Harbor Healthcare System & NYU School of Medicine, New York, NY 10016, USA. 8. Dr Miriam & Sheldon G Adelson Clinic for Drug Abuse Treatment & Research, Las Vegas, NV 89169, USA.
Abstract
AIM: This study was designed to determine whether polymorphisms in acetylcholine receptors contribute to opioid dependence and/or cocaine dependence. PATIENTS & METHODS: The sample (n = 1860) was divided by drug and ancestry, and 55 polymorphisms (nine genes) were analyzed. RESULTS: 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. CONCLUSION: Cholinergic receptors' variants may contribute to drug addiction and have a potential role as pharmacogenetic markers.
AIM: This study was designed to determine whether polymorphisms in acetylcholine receptors contribute to opioid dependence and/or cocaine dependence. PATIENTS & METHODS: The sample (n = 1860) was divided by drug and ancestry, and 55 polymorphisms (nine genes) were analyzed. RESULTS: 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. CONCLUSION: Cholinergic receptors' variants may contribute to drug addiction and have a potential role as pharmacogenetic markers.
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