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Further evidence of association between amphetamine response and SLC6A2 gene variants.

ABSTRACT: We previously found that the intronic norepinephrine transporter gene (SLC6A2) polymorphism rs36017 modulates feelings of elation after administration of 20 mg D-amphetamine in healthy volunteers.In this study, we further investigated the association between D-amphetamine response and 11 SLC6A2 single-nucleotide polymorphisms (SNPs), including rs36017, in an extended sample of Caucasian young adults.One hundred fifty-nine healthy volunteers participated in a three-session double-blind crossover design receiving either placebo or oral D-amphetamine (10 and 20 mg). Based on our previous results, we examined the associations between levels of self-reported elation and vigor after D-amphetamine administration and SNPs and SNP haplotypes in SLC6A2.Consistent with our previous findings, SNPs rs36017 and rs1861647 were associated with significantly higher ratings of elation and vigor after 20 mg Damphetamine. Ratings of vigor after 20 mg D-amphetamine were also associated with a two-SNP haplotype formed with rs1861647 and rs5569 and a three-SNP haplotype formed with rs36017, rs10521329, and rs3785155.These results provide further evidence that genetic variants in the SLC6A2 gene are involved in acute response to D-amphetamine, which may influence progression to amphetamine abuse. Identifying sources of variation in acute drug responses could lead to better prevention and treatment of psychostimulant abuse and may be valuable in the therapeutic use of stimulants.

SUBMITTER: Dlugos AM

PROVIDER: S-EPMC4242585 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Further evidence of association between amphetamine response and SLC6A2 gene variants.

Dlugos Andrea M AM Hamidovic Ajna A Palmer Abraham A AA de Wit Harriet H

Psychopharmacology 20091001 3

<h4>Background and rationale</h4>We previously found that the intronic norepinephrine transporter gene (SLC6A2) polymorphism rs36017 modulates feelings of elation after administration of 20 mg D-amphetamine in healthy volunteers.<h4>Objectives</h4>In this study, we further investigated the association between D-amphetamine response and 11 SLC6A2 single-nucleotide polymorphisms (SNPs), including rs36017, in an extended sample of Caucasian young adults.<h4>Methods</h4>One hundred fifty-nine health ...[more]

PMID: 19727679

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Project description:With the continuous rapid urbanization process over the last three decades, outdoors air pollution has become a progressively more serious public health hazard in China. To investigate the possible associations, lag effects and seasonal differences of urban air quality on respiratory health (allergic rhinitis) in Changchun, a city in Northeastern China, we carried out a time-series analysis of the incidents of allergic rhinitis (AR) from 2013 to 2015. Environmental monitoring showed that PM2.5 and PM10 were the major air pollutants in Changchun, followed by SO₂, NO₂ and O₃. The results also demonstrated that the daily concentrations of air pollutants had obvious seasonal differences. PM10 had higher daily mean concentrations in spring (May, dust storms), autumn (October, straw burning) and winter (November to April, coal burning). The mean daily number of outpatient AR visits in the warm season was higher than in the cold season. The prevalence of allergic rhinitis was significantly associated with PM2.5, PM10, SO₂ and NO₂, and the increased mobility was 10.2% (95% CI, 5.5%-15.1%), 4.9% (95% CI, 0.8%-9.2%), 8.5% (95% CI, -1.8%-19.8%) and 11.1% (95% CI, 5.8%-16.5%) for exposure to each 1-Standard Deviation (1-SD) increase of pollutant, respectively. Weakly or no significant associations were observed for CO and O₃. As for lag effects, the highest Relative Risks (RRs) of AR from SO₂, NO₂, PM10 and PM2.5 were on the same day, and the highest RR from CO was on day 4 (L4). The results also indicated that the concentration of air pollutants might contribute to the development of AR. To summarize, this study provides further evidence of the significant association between ambient particulate pollutants (PM2.5 and PM10, which are usually present in high concentrations) and the prevalence of respiratory effects (allergic rhinitis) in the city of Changchun, located in Northeastern China. Environmental control and public health strategies should be enforced to address this increasingly challenging problem.

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Further evidence of association between amphetamine response and SLC6A2 gene variants.

Publications

Further evidence of association between amphetamine response and SLC6A2 gene variants.

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