Abstract
Genome-wide studies provide increasing evidence of association of genetic variants with different behaviors. However, there is a growing need for replication and subsequent characterization of specific findings. In this sense, the CHRNA5 gene has been associated with nicotine (with genome-wide significance), alcohol and cocaine addictions. So far, this gene has not been evaluated in smoked (crack) cocaine. We aimed to analyze the influence of CHRNA5 variants in crack addiction susceptibility and severity. The sample includes 300 crack-addicted patients and 769 non-addicted individuals. The CHRNA5 SNPs evaluated were rs588765, rs16969968, and rs514743. Homozygosity for rs16969968 and rs588765 major alleles was nominally associated with a risk to crack addiction (GG, P = 0.032; CC, P = 0.036, respectively). Haplotype analyses reveal significant associations (rs588765|rs16969968|rs514743 pglobal-corrected = 7.66 × 10–5) and suggest a substantial role for rs16969968. These findings corroborate previous reports in cocaine addiction—in line with the expected effects of cocaine in the cholinergic system—and in the opposite direction of significant GWAS findings for nicotine addiction susceptibility. These results are strengthened by the first report of an association of rs588765 with crack addiction and by the haplotype findings. In summary, our study highlights the relevance of the α5 subunit on crack cocaine addiction, replicating previous results relating CHRNA5 with the genetics and pathophysiology of addiction of different drugs.
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Acknowledgements
We are thankful to the staff of the participating psychiatric units for all their support with data collection.
Funding
This study was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnologico (CNPq, 476529/2012-3, 466722/2014-1, 466802/2014-5 and 424041/2016-2), Coordenação de Aperfeiçoamento Pessoal de Nível Superior (CAPES, Finance Code 001), and Secretaria Nacional de Políticas sobre Drogas (SENAD, 82264/2015) and FIPE-HCPA. Any funding source had participation in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
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EHG was on the speaker's bureau for Novartis and Shire for the last 3 years. He also received travel awards (air tickets and hotel accommodations) for participating in two psychiatric meetings from Shire and Novartis. The remaining authors declare no conflict of interest.
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Aroche, A.P., Rovaris, D.L., Grevet, E.H. et al. Association of CHRNA5 Gene Variants with Crack Cocaine Addiction. Neuromol Med 22, 384–390 (2020). https://doi.org/10.1007/s12017-020-08596-1
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DOI: https://doi.org/10.1007/s12017-020-08596-1