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

Orna Levran, Matthew Randesi, Einat Peles, Joel Correa Da Rosa, Jurg Ott, John Rotrosen, Miriam Adelson, Mary Jeanne Kreek

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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.

Original languageEnglish
Pages (from-to)995-1003
Number of pages9
JournalPharmacogenomics
Volume17
Issue number9
DOIs
StatePublished - Jun 2016
Externally publishedYes

Keywords

  • African ancestry
  • CHRM4
  • cholinergic receptors
  • cocaine addiction
  • opioid addiction

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