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Logo of behbrainBioMed CentralBiomed Central Web Sitesearchsubmit a manuscriptregisterthis articleBehavioral and Brain Functions : BBFJournal Front Page
 
Behav Brain Funct. 2012; 8: 23.
Published online 2012 May 16. doi:  10.1186/1744-9081-8-23
PMCID: PMC3406967

Variation in regulator of G-protein signaling 17 gene (RGS17) is associated with multiple substance dependence diagnoses

Abstract

Background

RGS17 and RGS20 encode two members of the regulator of G-protein signaling RGS-Rz subfamily. Variation in these genes may alter their transcription and thereby influence the function of G protein-coupled receptors, including opioid receptors, and modify risk for substance dependence.

Methods

The association of 13 RGS17 and eight RGS20 tag single nucleotide polymorphisms (SNPs) was examined with four substance dependence diagnoses (alcohol (AD), cocaine (CD), opioid (OD) or marijuana (MjD)] in 1,905 African Americans (AAs: 1,562 cases and 343 controls) and 1,332 European Americans (EAs: 981 cases and 351 controls). Analyses were performed using both χ2 tests and logistic regression analyses that covaried sex, age, and ancestry proportion. Correlation of genotypes and mRNA expression levels was assessed by linear regression analyses.

Results

Seven RGS17 SNPs showed a significant association with at least one of the four dependence traits after a permutation-based correction for multiple testing (0.003≤Pempirical≤0.037). The G allele of SNP rs596359, in the RGS17 promoter region, was associated with AD, CD, OD, or MjD in both populations (0.005≤Pempirical≤0.019). This allele was also associated with significantly lower mRNA expression levels of RGS17 in YRI subjects (P = 0.002) and non-significantly lower mRNA expression levels of RGS17 in CEU subjects (P = 0.185). No RGS20 SNPs were associated with any of the four dependence traits in either population.

Conclusions

This study demonstrated that variation in RGS17 was associated with risk for substance dependence diagnoses in both AA and EA populations.

Keywords: RGS17 and RGS20, Multiple substance dependence, Genetic association, Haplotype analysis, Regression analysis, Genotype-expression relationship

Articles from Behavioral and Brain Functions : BBF are provided here courtesy of BioMed Central