Genetic and epigenetic analysis of the serotonin 2A receptor in the context of cocaine abuse.
Genetic and epigenetic analysis of the serotonin 2A receptor in the context of cocaine abuse.
复制标题
可卡因滥用背景下血清素 2A 受体的遗传和表观遗传分析。
DOI：
10.1080/15592294.2021.2005277
复制
发表时间：
2022
期刊：
影响因子：
3.7
通讯作者：
Smith,RyanM
中科院分区：
文献类型：
--
作者：
Alrfooh,Aysheh;Smith,RyanM
Despite more than 2 million American cocaine users monthly, there is no approved drug for treating cocaine use disorder. Cocaine use disorder has a multifactorial aetiology, including both genetic and environmental factors. Both cocaine use and genetic variations demonstrably alter DNA methylation and gene expression in the brain in a complex manner. How these factors interact in the context of cocaine abuse in humans is unknown. We propose that we can identify potential drug targets for treating cocaine use disorders by examining genetic, epigenetic, and expression changes in the brains of individuals that abused cocaine. In this study, we identified the interaction between the epigenetics changes (DNA CpG methylation) and genetic variants (SNPs) in theHTR2Agene in the context of cocaine addiction by using brain tissue collected from individuals that overdosed on cocaine (N = 14) and healthy matched controls (N = 16). We generated DNA CpG methylation profiles in eight regions ofHTR2Aharbouring frequent SNPs, measuring both allelic and total methylation, and compared these methylation profiles withHTR2AmRNA expression. Furthermore, we examined the influence of common variants rs6311 and rs6313 on cocaine abuse, methylation, and gene expression. We found evidence that rs6311 regulatesHTR2Amethylation, consistent with earlier studies. Furthermore, the minor alleles for rs6311 and rs6313 are associated with significantly increased expression of a splice isoform in which exon 2 is truncated in both cocaine and control samples. These results reveal specific roles forHTR2Ain the context of cocaine abuse, highlighting opportunities to modulate this target for treating cocaine use disorder.
