{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:50:46Z","timestamp":1760244646623,"version":"build-2065373602"},"reference-count":38,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,31]],"date-time":"2022-12-31T00:00:00Z","timestamp":1672444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Program for Genomic Medicine","award":["NSC 100-3112-B-400-015","NSC 100-2314-B-400-002-MY3","MOST 106-2320-B-400-012","NP-111, 112-SP-01, NP-111, 112-PP-03, NP-111, 112-PP-08, NP-111, 112-PP-09, and PH-111, 112-PP-02"],"award-info":[{"award-number":["NSC 100-3112-B-400-015","NSC 100-2314-B-400-002-MY3","MOST 106-2320-B-400-012","NP-111, 112-SP-01, NP-111, 112-PP-03, NP-111, 112-PP-08, NP-111, 112-PP-09, and PH-111, 112-PP-02"]}]},{"name":"National Science Council","award":["NSC 100-3112-B-400-015","NSC 100-2314-B-400-002-MY3","MOST 106-2320-B-400-012","NP-111, 112-SP-01, NP-111, 112-PP-03, NP-111, 112-PP-08, NP-111, 112-PP-09, and PH-111, 112-PP-02"],"award-info":[{"award-number":["NSC 100-3112-B-400-015","NSC 100-2314-B-400-002-MY3","MOST 106-2320-B-400-012","NP-111, 112-SP-01, NP-111, 112-PP-03, NP-111, 112-PP-08, NP-111, 112-PP-09, and PH-111, 112-PP-02"]}]},{"DOI":"10.13039\/501100006245","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["NSC 100-3112-B-400-015","NSC 100-2314-B-400-002-MY3","MOST 106-2320-B-400-012","NP-111, 112-SP-01, NP-111, 112-PP-03, NP-111, 112-PP-08, NP-111, 112-PP-09, and PH-111, 112-PP-02"],"award-info":[{"award-number":["NSC 100-3112-B-400-015","NSC 100-2314-B-400-002-MY3","MOST 106-2320-B-400-012","NP-111, 112-SP-01, NP-111, 112-PP-03, NP-111, 112-PP-08, NP-111, 112-PP-09, and PH-111, 112-PP-02"]}],"id":[{"id":"10.13039\/501100006245","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Health Research Institutes, Taiwan","award":["NSC 100-3112-B-400-015","NSC 100-2314-B-400-002-MY3","MOST 106-2320-B-400-012","NP-111, 112-SP-01, NP-111, 112-PP-03, NP-111, 112-PP-08, NP-111, 112-PP-09, and PH-111, 112-PP-02"],"award-info":[{"award-number":["NSC 100-3112-B-400-015","NSC 100-2314-B-400-002-MY3","MOST 106-2320-B-400-012","NP-111, 112-SP-01, NP-111, 112-PP-03, NP-111, 112-PP-08, NP-111, 112-PP-09, and PH-111, 112-PP-02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms24010721","type":"journal-article","created":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T04:17:38Z","timestamp":1672633058000},"page":"721","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Splice-Site Variants in the Gene Encoding GABA-A Receptor Delta Subunit Are Associated with Amphetamine Use in Patients under Methadone Maintenance Treatment"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3017-6026","authenticated-orcid":false,"given":"Yen-Feng","family":"Lin","sequence":"first","affiliation":[{"name":"Center for Neuropsychiatric Research, National Health Research Institutes, 35 Keyan Road, Zhunan Town, Miaoli County 350, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Hai","family":"Chou","sequence":"additional","affiliation":[{"name":"Center for Neuropsychiatric Research, National Health Research Institutes, 35 Keyan Road, Zhunan Town, Miaoli County 350, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tung-Hsia","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Neuropsychiatric Research, National Health Research Institutes, 35 Keyan Road, Zhunan Town, Miaoli County 350, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiu-Ping","family":"Fang","sequence":"additional","affiliation":[{"name":"Center for Neuropsychiatric Research, National Health Research Institutes, 35 Keyan Road, Zhunan Town, Miaoli County 350, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsiang-Wei","family":"Kuo","sequence":"additional","affiliation":[{"name":"Center for Neuropsychiatric Research, National Health Research Institutes, 35 Keyan Road, Zhunan Town, Miaoli County 350, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0365-3587","authenticated-orcid":false,"given":"Po-Hsiu","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Public Health & Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei 100, Taiwan"},{"name":"Department of Psychiatry, National Taiwan University Hospital, Taipei 100, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shih-Jen","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Taipei Veterans General Hospital, Taipei 112, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheng-Chang","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Neuropsychiatric Research, National Health Research Institutes, 35 Keyan Road, Zhunan Town, Miaoli County 350, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ren-Hua","family":"Chung","sequence":"additional","affiliation":[{"name":"Institute of Population Health Sciences, National Health Research Institutes, Miaoli County 350, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6773-4111","authenticated-orcid":false,"given":"Hsiao-Hui","family":"Tsou","sequence":"additional","affiliation":[{"name":"Institute of Population Health Sciences, National Health Research Institutes, Miaoli County 350, Taiwan"},{"name":"Graduate Institute of Biostatistics, College of Public Health, China Medical University, Taichung 404, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1376-8505","authenticated-orcid":false,"given":"Andrew C. 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