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

Pharmacogenomics. 2016 Jun;17(9):995-1003. doi: 10.2217/pgs-2016-0028. Epub 2016 Jun 7.


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.

Keywords: African ancestry; CHRM4; cholinergic receptors; cocaine addiction; opioid addiction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • African Continental Ancestry Group / genetics*
  • Chromosomes, Human, Pair 11 / genetics
  • Cocaine-Related Disorders / genetics*
  • Diacylglycerol Kinase / genetics
  • European Continental Ancestry Group / genetics
  • Genetic Variation*
  • Heroin Dependence / genetics*
  • Humans
  • Linkage Disequilibrium
  • Polymorphism, Genetic / genetics
  • Polymorphism, Single Nucleotide
  • Receptor, Muscarinic M4
  • Receptors, Muscarinic / genetics*
  • Schizophrenia / genetics


  • AMBRA1 protein, human
  • Adaptor Proteins, Signal Transducing
  • CHRM4 protein, human
  • Receptor, Muscarinic M4
  • Receptors, Muscarinic
  • Diacylglycerol Kinase
  • diacylglycerol kinase zeta, human