Background: RGS17 and RGS20 encode two members of the regulator of G-protein signaling RGS-Rz subfamily.\r\nVariation in these genes may alter their transcription and thereby influence the function of G protein-coupled\r\nreceptors, including opioid receptors, and modify risk for substance dependence.\r\nMethods: The association of 13 RGS17 and eight RGS20 tag single nucleotide polymorphisms (SNPs) was examined\r\nwith four substance dependence diagnoses (alcohol (AD), cocaine (CD), opioid (OD) or marijuana (MjD)] in 1,905\r\nAfrican Americans (AAs: 1,562 cases and 343 controls) and 1,332 European Americans (EAs: 981 cases and 351\r\ncontrols). Analyses were performed using both ?2 tests and logistic regression analyses that covaried sex, age, and\r\nancestry proportion. Correlation of genotypes and mRNA expression levels was assessed by linear regression\r\nanalyses.\r\nResults: Seven RGS17 SNPs showed a significant association with at least one of the four dependence traits after a\r\npermutation-based correction for multiple testing (0.003=Pempirical=0.037). The G allele of SNP rs596359, in the\r\nRGS17 promoter region, was associated with AD, CD, OD, or MjD in both populations (0.005=Pempirical=0.019).\r\nThis allele was also associated with significantly lower mRNA expression levels of RGS17 in YRI subjects\r\n(P = 0.002) and non-significantly lower mRNA expression levels of RGS17 in CEU subjects (P = 0.185). No RGS20\r\nSNPs were associated with any of the four dependence traits in either population.\r\nConclusions: This study demonstrated that variation in RGS17 was associated with risk for substance\r\ndependence diagnoses in both AA and EA populations.
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