title: Overlapping dopaminergic pathway genetic susceptibility to heroin and cocaine addictions in African Americans.
abstract: Drugs of abuse activate the mesolimbic dopaminergic pathway. Genetic variations in the dopaminergic system may contribute to drug addiction. Several processes are shared between cocaine and heroin addictions but some neurobiological mechanisms may be specific. This study examined the association of 98 single nucleotide polymorphisms in 13 dopamine-related genes with heroin addiction (OD) and/or cocaine addiction (CD) in a sample of 801 African Americans (315 subjects with OD ± CD, 279 subjects with CD, and 207 controls). Single-marker analyses provided nominally significant evidence for associations of 24 SNPs) in DRD1, ANKK1/DRD2, DRD3, DRD5, DBH, DDC, COMT and CSNK1E. A DRD2 7-SNPs haplotype that includes SNPs rs1075650 and rs2283265, which were shown to alter D2S/D2L splicing, was indicated in both addictions. The Met allele of the functional COMT Val158Met was associated with protection from OD. None of the signals remained significant after correction for multiple testing. The study results are in accordance with the results of previous studies, including our report of association of DRD1 SNP rs5326 with OD. The findings suggest the presence of an overlap in genetic susceptibility for OD and CD, as well as shared and distinct susceptibility for OD in subjects of African and European descent.
authors: The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY, USA.
authors: Orna
authors: O
authors: Levran
authors: Matthew
authors: M
authors: Randesi
authors: Joel Correa
authors: JC
authors: da Rosa
authors: Jurg
authors: J
authors: Ott
authors: John
authors: J
authors: Rotrosen
authors: Miriam
authors: M
authors: Adelson
authors: Mary Jeanne
authors: MJ
authors: Kreek
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics; D000368:Aged; D016022:Case-Control Studies; D019970:Cocaine-Related Disorders / Q000235:genetics*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006556:Heroin Dependence / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins
keywords: African Americans; COMT Val158Met; DRD1; DRD2; Dopaminergic pathway; cocaine addiction; heroin addiction; polymorphism; rs1075650; rs2283265; rs5326