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

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.