African-specific variability in the acetylcholine muscarinic receptor M4: association with cocaine and heroin addiction

被引：10
作者：
Levran, Orna [1 ]
Randesi, Matthew [1 ]
Peles, Einat [2 ,3 ]
da Rosa, Joel Correa [4 ]
Ott, Jurg [5 ,6 ]
Rotrosen, John [7 ,8 ]
Adelson, Miriam [1 ,2 ,9 ]
Kreek, Mary Jeanne [1 ]
机构：
[1] Rockefeller Univ, Lab Biol Addict Dis, New York, NY 10065 USA
[2] Tel Aviv Elias Sourasky Med Ctr, Dr Miriam & Sheldon G Adelson Clin Drug Abuse Tre, Tel Aviv, Israel
[3] Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel
[4] Rockefeller Univ, Ctr Clin & Translat Sci, New York, NY 10065 USA
[5] Chinese Acad Sci, Inst Psychol, Beijing, Peoples R China
[6] Rockefeller Univ, Lab Stat Genet, New York, NY 10065 USA
[7] VA New York Harbor Healthcare Syst, New York, NY 10016 USA
[8] NYU, Sch Med, New York, NY 10016 USA
[9] Dr Miriam & Sheldon G Adelson Clin Drug Abuse Tre, Las Vegas, NV 89169 USA
来源：
PHARMACOGENOMICS | 2016年 / 17卷 / 09期
关键词：
African ancestry; cholinergic receptors; CHRM4; cocaine addiction; opioid addiction; NICOTINE DEPENDENCE; CHRM2; GENE; ALCOHOL DEPENDENCE; DRUG-DEPENDENCE; POLYMORPHISMS; SUSCEPTIBILITY; DISORDERS; TRANSMISSION; NEUROBIOLOGY; PREDISPOSES;
D O I：
10.2217/pgs-2016-0028
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
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 (P-corrected = 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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收藏
页码：995 / 1003
页数：9
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