African-specific variability in the acetylcholine muscarinic receptor M4: association with cocaine and heroin addiction. (June 2016)

• Record Type: Journal Article
• Authors: Levran, Orna; Randesi, Matthew; Peles, Einat; Correa da Rosa, Joel; Ott, Jurg; Rotrosen, John; Adelson, Miriam; Kreek, Mary Jeanne
• Is Part Of: Pharmacogenomics. Volume 17:Number 9(2016)
• Page Start: 995
• Page End: 1003
• Publication Date: 2016-06
• Subjects: African ancestry -- cholinergic receptors -- CHRM4 -- cocaine addiction -- opioid addiction; Pharmacogenomics -- Periodicals; 615.1
• DOI: 10.2217/pgs-2016-0028
• Languages: English
• ISSNs: 1462-2416

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.