Ishiguro H, Saito T, Akazawa S, Mitushio H, Tada K, Enomoto M, Mifune H, Toru M, Shibuya H, Arinami T
Department of Medical Genetics, Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki, Japan.
Alcohol Clin Exp Res. 1999 Jul;23(7):1281-4.
Involvement of the serotoninergic system (S/S) in alcoholism has been suggested in both mice and humans. Previous studies have suggested the S/S genotype of the serotonin transporter gene promoter polymorphism to be associated with severe alcohol dependence marked by severe withdrawal symptoms. It has also been associated with alcoholics who exhibit a dissocial personality disorder.
We examined the polymorphism in 166 Japanese alcoholics who experienced withdrawal seizure or delirium and 290 Japanese controls.
The S/S genotype was not increased in the patients. Exploratory analyses showed significantly less frequent S allele and S/S genotype frequencies in the alcoholics with a history of drinking-related arrests than in the controls (p = 0.009 and p = 0.03, respectively), perhaps reflecting previously reported harm avoidance personality traits associated with S/S. Alcoholics with the L allele had a significantly earlier onset of alcohol dependence than those with the S/S genotype (p = 0.01).
The present study failed to provide supportive evidence for an association of the S/S genotype with severe alcoholism marked by physical withdrawal symptoms or with antisocial behaviors among the Japanese. Although our data support involvement of the central serotoninergic system in some types of alcoholism, the potential association findings of this study emerged as only exploratory and, therefore, should be understood as tentative until replicated in other studies.
在小鼠和人类研究中均提示血清素能系统(S/S)与酒精中毒有关。既往研究表明,血清素转运体基因启动子多态性的S/S基因型与以严重戒断症状为特征的严重酒精依赖有关。它还与表现出反社会人格障碍的酗酒者有关。
我们检测了166名经历过戒断性癫痫发作或谵妄的日本酗酒者以及290名日本对照者的多态性。
患者中S/S基因型并未增加。探索性分析显示,有饮酒相关被捕史的酗酒者中S等位基因和S/S基因型频率显著低于对照组(分别为p = 0.009和p = 0.03),这可能反映了先前报道的与S/S相关的避免伤害人格特质。携带L等位基因的酗酒者酒精依赖发病时间显著早于携带S/S基因型的酗酒者(p = 0.01)。
本研究未能为S/S基因型与以身体戒断症状为特征的严重酒精中毒或与日本人的反社会行为之间的关联提供支持性证据。尽管我们的数据支持中枢血清素能系统参与某些类型的酒精中毒,但本研究的潜在关联结果仅为探索性的,因此,在其他研究重复验证之前应视为初步结论。