Mubumbila Victor, Sutter Anne, Ptok Ursula, Heun Reinhard, Quirin-Stricker Christiane
Laboratoire de Génétique Moléculaire des Eucaryotes-CNRS, Unité 184 de Biologie Moléculaire et de Génie Génétique-INSERM, Faculté de Médecine, 11 rue Humann, 67085 Strasbourg, France.
Neurosci Lett. 2002 Nov 15;333(1):9-12. doi: 10.1016/s0304-3940(02)00955-2.
The dysfunction of the cholinergic system in Alzheimer's disease (AD) supports the hypothesis that a decline in choline acetyltransferase (ChAT) activity in memory as well as in cognitive functions in AD might be functionally linked. To assess the physiological relevance of an allelic variation in the ChAT gene we investigated the presence of a possible polymorphism in AD patients and in elderly non-demented subjects as controls. By using polymerase chain reaction, single stranded conformation polymorphism or the LightCycler analysis we detected a single nucleotide polymorphism in the first common coding exon of the ChAT gene. We found a G --> A transition which occurred at position +4 of the coding sequence. The association between AD and the AA genotype or A alleles were found to be significant (odds ratio 3.7 and 2.4, respectively). The frequency of the AA genotype was three times higher in AD patients than in age-matched controls. This G --> A change raises the possibility that it may influence ATG usage resulting in attenuation of translation efficacy of ChAT messenger RNA. We suggest that such a polymorphism might be one of the events conferring an increased risk for deterioration of memory and cognition functions in AD.
阿尔茨海默病（AD）中胆碱能系统的功能障碍支持了这样一种假说，即AD患者记忆以及认知功能中胆碱乙酰转移酶（ChAT）活性的下降可能在功能上存在关联。为了评估ChAT基因等位基因变异的生理相关性，我们研究了AD患者以及作为对照的老年非痴呆受试者中是否存在可能的多态性。通过使用聚合酶链反应、单链构象多态性或LightCycler分析，我们在ChAT基因的第一个常见编码外显子中检测到一个单核苷酸多态性。我们发现一个G→A的转换发生在编码序列的+4位置。发现AD与AA基因型或A等位基因之间的关联具有显著性（优势比分别为3.7和2.4）。AD患者中AA基因型的频率比年龄匹配的对照组高3倍。这种G→A的变化增加了它可能影响起始密码子使用从而导致ChAT信使核糖核酸翻译效率降低的可能性。我们认为这种多态性可能是导致AD患者记忆和认知功能恶化风险增加的事件之一。
