Pharmacogenomics · 2016
African-specific variability in the acetylcholine muscarinic receptor M4: association with cocaine and heroin addiction.
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Levran Orna, Randesi Matthew, Peles Einat, Correa da Rosa Joel, Ott Jurg, Rotrosen John, Adelson Miriam, Kreek Mary Jeanne
Аннотация
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.
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.
Предметные рубрики MeSH
Adaptor Proteins, Signal TransducingBlack PeopleChromosomes, Human, Pair 11Cocaine-Related DisordersDiacylglycerol KinaseGenetic VariationHeroin DependenceHumansLinkage DisequilibriumPolymorphism, GeneticPolymorphism, Single NucleotideReceptor, Muscarinic M4Receptors, MuscarinicSchizophreniaWhite People