Biermann T, Reulbach U, Lenz B, Muschler M, Sperling W, Hillemacher T, Kornhuber J, Bleich S
Department of Psychiatry and Psychotherapy, University Hospital of Erlangen, Schwabachanlage 6, D-91054 Erlangen, Germany.
Alcohol. 2009 Mar;43(2):91-5. doi: 10.1016/j.alcohol.2008.12.008.
Chronic alcoholism is associated with hyperhomocysteinemia. Herp (homocysteine-induced endoplasmic reticulum [ER] protein) levels are elevated as a response to ER stress prior to mitochondrial dysfunction and cell death. The Lesch classification system has been applied in many studies and has been found useful. This study was undertaken to assess Herp mRNA expression in actively drinking patients with alcoholism who were classified according to Lesch's typology. Herp mRNA expression levels were measured by quantitative PCR in the blood of 76 male alcoholic patients. Patients were classified according to Lesch's typology (type I-IV). With respect to Lesch's typology, a significant difference in Herp mRNA expression regarding the four subtypes could be shown (F[3,72]=2.83, P=.044). In a logistic regression model (dependent variable Herp dichotomized by a median-split; adjusted for age and homocysteine levels) the subtype II differed statistically significant from the others (odds ratio, 5.75; 95% confidence interval, 2.07-15.98; P=.001). Type II alcoholic patients had a statistically significant higher expression of Herp mRNA due to upregulation of the expression of this neuroprotective cell non-chaperone by toxic effects of ethanol. These findings might explain why type II patients do not express severe withdrawal symptomatology (i.e., withdrawal seizures). These findings may be useful in the understanding and treatment considerations of different subtypes of alcohol dependence.
慢性酒精中毒与高同型半胱氨酸血症有关。在出现线粒体功能障碍和细胞死亡之前，作为对内质网（ER）应激的一种反应，同型半胱氨酸诱导的内质网（ER）蛋白（Herp）水平会升高。Lesch分类系统已在许多研究中应用，并被发现是有用的。本研究旨在评估根据Lesch分型法分类的正在饮酒的酒精中毒患者中Herp mRNA的表达情况。通过定量PCR测量了76名男性酒精中毒患者血液中的Herp mRNA表达水平。患者根据Lesch分型法（I-IV型）进行分类。关于Lesch分型法，四种亚型的Herp mRNA表达存在显著差异（F[3,72]=2.83，P=0.044）。在一个逻辑回归模型中（因变量Herp经中位数分割二分法；校正年龄和同型半胱氨酸水平），II型与其他亚型在统计学上有显著差异（优势比，5.75；95%置信区间，2.07-15.98；P=0.001）。II型酒精中毒患者由于乙醇的毒性作用上调了这种神经保护细胞非伴侣蛋白的表达，其Herp mRNA表达在统计学上显著更高。这些发现可能解释了为什么II型患者不表现出严重的戒断症状（即戒断性癫痫发作）。这些发现可能有助于理解和考虑酒精依赖不同亚型的治疗。
