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波兰酒精依赖患者及其家庭中谷氨酸受体GRIK3基因Ser310Ala多态性的家系研究和病例对照关联研究

Family-based and case-control association studies of glutamate receptor GRIK3 Ser310Ala polymorphism in Polish patients and families with alcohol dependence.

作者信息

Samochowiec Jerzy, Grzywacz Anna, Kucharska-Mazur Jolanta, Samochowiec Agnieszka, Horodnicki Jan, Pelka-Wysiecka Justyna, Syrek Szymon

机构信息

Department of Psychiatry, Pomeranian Medical University, Broniewskiego 26, 71-460 Szczecin, Poland.

出版信息

Neurosci Lett. 2006 Mar 27;396(2):159-62. doi: 10.1016/j.neulet.2005.11.030. Epub 2005 Dec 13.

Abstract

The aim of this study was to evaluate the role of the GRIK3 functional polymorphism (Ser310Ala) in the pathogenesis of alcoholism. This polymorphism was investigated in two types of studies: (1) the association study in a whole group of alcoholics (116 patients fulfilling ICD-10 alcohol dependence (AD) criteria and 255 controls, Polish descent) and homogenous overlapping subgroups of patients with: a history of delirium tremens and/or alcohol seizures, early age of onset of alcoholism (AOO<26 years), a co-occurrence of dissocial personality disorder, a history of familial alcoholism; (2) the family-based study (using Transmission Disequilibrium Test (TDT) in 100 Polish families with alcohol dependence). The history of alcoholism was obtained using SSAGA (Polish version). GRIK3 functional polymorphism was determined using PCR. TDT revealed an adequate transmission of both alleles to the affected offspring in the whole group of alcohol families (29 x Ser, 24 x Ala; chi2=0.472; d.f.=1; p=0.492) and in the homogenous subgroups of families. No significant associations between any of the above mentioned alcohol phenotypes and Ser310 allele were observed (the whole AD group: p=0.66 AD with delirium and/or seizures: p=0.521; early onset AD: p=0.868; AD with familial history of alcoholism: p=0.798 and AD with dissocial personality disorder: p=0.618). These findings do not seem to support the hypothesis of the role of this polymorphism in the pathogenesis of alcoholism.

摘要

本研究的目的是评估GRIK3功能多态性(Ser310Ala)在酒精中毒发病机制中的作用。在两类研究中对这种多态性进行了调查:(1)对一组酒精中毒患者(116例符合ICD - 10酒精依赖(AD)标准的患者和255名对照,波兰血统)以及具有以下特征的患者的同质重叠亚组进行关联研究:有震颤谵妄和/或酒精性癫痫发作史、酒精中毒发病年龄早(AOO<26岁)、共患反社会人格障碍、有家族性酒精中毒史;(2)基于家庭的研究(在100个有酒精依赖的波兰家庭中使用传递不平衡检验(TDT))。使用SSAGA(波兰语版本)获取酒精中毒病史。使用PCR确定GRIK3功能多态性。TDT显示在整个酒精家庭组(29个Ser,24个Ala;chi2 = 0.472;自由度 = 1;p = 0.492)以及家庭的同质亚组中,两个等位基因均充分传递给患病后代。未观察到上述任何酒精表型与Ser310等位基因之间存在显著关联(整个AD组:p = 0.66;有震颤谵妄和/或癫痫发作的AD:p = 0.521;早发性AD:p = 0.868;有酒精中毒家族史的AD:p = 0.798;有反社会人格障碍的AD:p = 0.618)。这些发现似乎不支持这种多态性在酒精中毒发病机制中起作用的假设。

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