Drug addiction and stress-response genetic variability: association study in African Americans.
Stress is a significant risk factor in the development of drug addictions and in addiction relapse susceptibility. This hypothesis-driven study was designed to determine if specific SNPs in genes related to stress response are associated with heroin and/or cocaine addiction in African Americans. The analysis included 27 genes (124 SNPs) and was performed independently for each addiction. The sample consisted of former heroin addicts in methadone maintenance treatment (n = 314), cocaine addicts (n = 281), and controls (n = 208). Fourteen SNPs showed nominally significant association with heroin addiction (p < 0.05), including the African-specific, missense SNP rs5376 (Asn334Ser) in the galanin receptor type 1 gene (GALR1) and the functional FKBP5 intronic SNP rs1360780. Thirteen SNPs showed association with cocaine addiction, including the synonymous SNPs rs237902, in the oxytocin receptor gene (OXTR), and rs5374 in GALR1. No signal remained significant after correction for multiple testing. Four additional SNPs (GALR1 rs2717162, AVP rs2282018, CRHBP rs1875999, and NR3C2 rs1040288) were associated with both addictions and may indicate common liability. The study provides preliminary evidence for novel association of variants in several stress-related genes with heroin and/or cocaine addictions and may enhance the understanding of the interaction between stress and addictions.
The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY, USA.
Orna
O
Levran
Matthew
M
Randesi
Yi
Y
Li
John
J
Rotrosen
Jurg
J
Ott
Miriam
M
Adelson
Mary Jeanne
MJ
Kreek
D001741:Black or African American / Q000235:genetics*; D016022:Case-Control Studies; D019295:Computational Biology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D013312:Stress, Physiological / Q000235:genetics*; D013315:Stress, Psychological / Q000235:genetics*; D019966:Substance-Related Disorders / Q000209:etiology*
AVP; African Americans; FKBP5; GALR1; HPA axis; Heroin addiction; NR3C2; OXTR; cocaine addiction; stress