Association of CHRNA5 Gene Variants with Crack Cocaine Addiction
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 signi...
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Veröffentlicht in: | Neuromolecular medicine 2020-09, Vol.22 (3), p.384-390 |
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Zusammenfassung: | 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 p
global-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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ISSN: | 1535-1084 1559-1174 |
DOI: | 10.1007/s12017-020-08596-1 |