Splice-Site Variants in the Gene Encoding GABA-A Receptor Delta Subunit Are Associated with Amphetamine Use in Patients under Methadone Maintenance Treatment

被引:1
|
作者
Lin, Yen-Feng [1 ]
Chou, Wen-Hai [1 ]
Liu, Tung-Hsia [1 ]
Fang, Chiu-Ping [1 ]
Kuo, Hsiang-Wei [1 ]
Kuo, Po-Hsiu [2 ,3 ,4 ]
Tsai, Shih-Jen [5 ]
Wang, Sheng-Chang [1 ]
Chung, Ren-Hua [6 ]
Tsou, Hsiao-Hui [6 ,7 ]
Chen, Andrew C. H. [8 ,9 ]
Liu, Yu-Li [1 ,10 ]
机构
[1] Natl Hlth Res Inst, Ctr Neuropsychiat Res, 35 Keyan Rd, Zhunan Town 350, Miaoli County, Taiwan
[2] Natl Taiwan Univ, Dept Publ Hlth, Taipei 100, Taiwan
[3] Natl Taiwan Univ, Inst Epidemiol & Prevent Med, Taipei 100, Taiwan
[4] Natl Taiwan Univ Hosp, Dept Psychiat, Taipei 100, Taiwan
[5] Taipei Vet Gen Hosp, Dept Psychiat, Taipei 112, Taiwan
[6] Natl Hlth Res Inst, Inst Populat Hlth Sci, Zhunan Town 350, Miaoli County, Taiwan
[7] China Med Univ, Grad Inst Biostat, Coll Publ Hlth, Taichung 404, Taiwan
[8] Northwell Hlth, Zucker Hillside Hosp, Dept Psychiat, New York, NY 11004 USA
[9] Donald & Barbara Zucker Sch Med Hofstra Northwell, Dept Psychiat, New York, NY 11549 USA
[10] China Med Univ, Grad Inst Clin Med Sci, Taichung 404, Taiwan
关键词
amphetamine use; GABRD; methadone maintenance treatment; psychostimulant; polysubstance abuse; IMMUNOCYTOCHEMICAL DISTRIBUTION; WITHDRAWAL SYMPTOMS; RAT-BRAIN; POLYMORPHISMS; METHAMPHETAMINE; PLASMA; HIPPOCAMPUS; HEROIN;
D O I
10.3390/ijms24010721
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
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.
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页数:11
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