https://scholars.lib.ntu.edu.tw/handle/123456789/628373
標題: | Splice-Site Variants in the Gene Encoding GABA-A Receptor Delta Subunit Are Associated with Amphetamine Use in Patients under Methadone Maintenance Treatment | 作者: | Lin, Yen-Feng Chou, Wen-Hai Liu, Tung-Hsia Fang, Chiu-Ping Kuo, Hsiang-Wei PO-HSIU KUO Tsai, Shih-Jen Wang, Sheng-Chang Chung, Ren-Hua Tsou, Hsiao-Hui Chen, Andrew C H Liu, Yu-Li |
關鍵字: | GABRD; amphetamine use; methadone maintenance treatment; polysubstance abuse; psychostimulant | 公開日期: | 31-十二月-2022 | 出版社: | MDPI | 卷: | 24 | 期: | 1 | 來源出版物: | International Journal of Molecular Sciences | 摘要: | Chronic opioid use disorder patients often also use other substances such as amphetamines. The gene-based analysis method was applied in the genomic database obtained from our previous study with 343 methadone maintenance treatment (MMT) patients. We found that the gene encoding gamma-aminobutyric acid type A receptors (GABA-A receptor) delta subunit isoforms (GABRD) was associated with amphetamine use in heroin dependent patients under MMT in Taiwan. A total of 15% of the 343 MMT patients tested positive for amphetamine in the urine toxicology test. Two genetic variants in the GABRD, rs2889475 and rs2376805, were found to be associated with the positive urine amphetamine test. They are located in the exon 1 of the splice variant and altered amino acid compositions (T126I, C/T, for rs2889475, and R252Q, G/A, for rs2376805). The CC genotype carriers of rs2889475 showed a four times higher risk of amphetamine use than those with TT genotype. The GG genotype carriers of rs2376805 showed a three times higher risk of amphetamine use than the AA genotype carriers. To our knowledge, this is the first report that demonstrated an association of the delta splice variant isoform in the GABA-A receptor with an increased risk of amphetamine use in MMT patients. Our results suggest that rs2889475 and rs2376805 may be indicators for the functional role and risk of amphetamine use in MMT patients. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/628373 | ISSN: | 16616596 | DOI: | 10.3390/ijms24010721 |
顯示於: | 流行病學與預防醫學研究所 |
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