Kim Sung-Gon, Kim Cheol-Min, Choi Sam-Wook, Jae Young-Myo, Lee Hae-Gook, Son Bong-Ki, Kim Jeong-Gee, Choi Young-Sung, Kim Han-Oh, Kim Seong-Yeon, Oslin David W
Department of Psychiatry, School of Medicine, Pusan National University, and Bongseng Memorial Hospital, 1-ga 10, Ami-dong, Seo-gu, Pusan, 602-739, South Korea.
Psychopharmacology (Berl). 2009 Jan;201(4):611-8. doi: 10.1007/s00213-008-1330-5. Epub 2008 Sep 16.
Previous studies have demonstrated an association between genetic polymorphisms of the mu opioid receptor gene (OPRM1) and response to naltrexone treatment. The Asp40 variant genotype previously shown to be associated with naltrexone treatment response is known to be relatively common among Koreans.
This study was conducted to prospectively investigate the relationship between genotype and response to open-label naltrexone treatment in Korean alcohol-dependent subjects.
Sixty-three alcohol-dependent subjects were prescribed naltrexone for 12 weeks in combination with cognitive behavioral therapy. Thirty-two subjects were adherent, taking the medication at least 80% of the treatment days [16 Asn40 (A/A) patients and 16 Asp40 variant (A/G or G/G) patients].
Subjects adherent to naltrexone treatment with one or two copies of the Asp40 allele took a significantly longer time than the Asn40 group to relapse (p=0.014). Although not significant, the Asn40 group treated with naltrexone had a 10.6 times greater relapse rate than the Asp40 variant group. There was no significant difference between the Asn40 group and the Asp40 variant group treated with naltrexone in rates of abstinence.
These results demonstrating a higher therapeutic effect of naltrexone in Korean alcohol-dependent individuals with the Asp40 variant genotype than the Asn40 genotype are consistent with previous study results in individuals of European descent. This is the first study to examine the pharmacogenetics treatment response to naltrexone in non-European subjects.
先前的研究已经证明μ阿片受体基因（OPRM1）的基因多态性与纳曲酮治疗反应之间存在关联。先前显示与纳曲酮治疗反应相关的Asp40变异基因型在韩国人中相对常见。
本研究旨在前瞻性调查韩国酒精依赖受试者的基因型与开放标签纳曲酮治疗反应之间的关系。
63名酒精依赖受试者被处方纳曲酮12周，并结合认知行为疗法。32名受试者坚持服药，在至少80%的治疗天数服用药物[16名Asn40（A/A）患者和16名Asp40变异型（A/G或G/G）患者]。
携带一份或两份Asp40等位基因且坚持纳曲酮治疗的受试者比Asn40组复发所需时间显著更长（p=0.014）。虽然不显著，但接受纳曲酮治疗的Asn40组复发率比Asp40变异型组高10.6倍。接受纳曲酮治疗的Asn40组和Asp40变异型组在戒酒率方面没有显著差异。
这些结果表明，在韩国酒精依赖个体中，Asp40变异基因型的人使用纳曲酮的治疗效果高于Asn40基因型，这与先前对欧洲血统个体的研究结果一致。这是第一项研究非欧洲受试者对纳曲酮的药物遗传学治疗反应的研究。
