| Summary: | <p>Abstract</p> <p>Background</p> <p><it>RGS17</it> and <it>RGS20</it> 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.</p> <p>Methods</p> <p>The association of 13 <it>RGS17</it> and eight <it>RGS20</it> 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 <it>χ</it><sup>2</sup> 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.</p> <p>Results</p> <p>Seven <it>RGS17</it> SNPs showed a significant association with at least one of the four dependence traits after a permutation-based correction for multiple testing (0.003≤<it>P</it><sub><it>empirical</it></sub>≤0.037). The G allele of SNP rs596359, in the <it>RGS17</it> promoter region, was associated with AD, CD, OD, or MjD in both populations (0.005≤<it>P</it><sub><it>empirical</it></sub>≤0.019). This allele was also associated with significantly lower mRNA expression levels of <it>RGS17</it> in YRI subjects (<it>P</it> = 0.002) and non-significantly lower mRNA expression levels of <it>RGS17</it> in CEU subjects (<it>P</it> = 0.185). No <it>RGS20</it> SNPs were associated with any of the four dependence traits in either population.</p> <p>Conclusions</p> <p>This study demonstrated that variation in <it>RGS17</it> was associated with risk for substance dependence diagnoses in both AA and EA populations.</p>
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