Department of Neurology, Qingdao Municipal Hospital, Dalian Medical University, China.
Neurosci Lett. 2013 Oct 25;554:162-6. doi: 10.1016/j.neulet.2013.09.006. Epub 2013 Sep 11.
COMT (catechol-O-methyltransferase) has been conjectured to be associated with Alzheimer's disease (AD) due to its key role in cognitive function impairment by influencing the dopamine degradation in prefrontal cortex. A functional single nucleotide polymorphism (rs4680 SNP; G to A) in the COMT coding region causes Val158Met amino acid substitution in the corresponding protein, with Val allele exhibiting markedly 3- to 4-fold higher than Met in enzyme activity. Recent study reported that the functional rs4680 polymorphism within COMT gene was associated with susceptibility to AD in Caucasians. In order to examine the association between polymorphism in COMT gene and late-onset AD (LOAD) in a Han Chinese group, we analyzed the genotype and allele distributions of the COMT rs4680 polymorphism in a Han Chinese population consisting of 2291 individuals (1132 LOAD patients and 1159 healthy controls). In the present study, we find no significant association between the COMT rs4680 polymorphism and LOAD, even after statistical adjustment for age, gender and apolipoprotein E (APOE) status in the total sample as well as stratification for APOE status. Our results indicated that the COMT Val158Met polymorphism may not play a major role in the development of LOAD in Han Chinese.
儿茶酚氧位甲基转移酶（COMT）因其在认知功能障碍中的关键作用而被认为与阿尔茨海默病（AD）有关，通过影响前额叶皮层中的多巴胺降解。COMT 编码区的功能性单核苷酸多态性（rs4680 SNP；G 到 A）导致相应蛋白质中 Val158Met 氨基酸取代，Val 等位基因表现出明显的 3-4 倍高于 Met 的酶活性。最近的研究报道，COMT 基因内的功能性 rs4680 多态性与白种人中 AD 的易感性有关。为了研究 COMT 基因多态性与汉族人群迟发性 AD（LOAD）之间的关系，我们分析了汉族人群中 COMT rs4680 多态性的基因型和等位基因分布，该人群包括 2291 人（1132 例 LOAD 患者和 1159 例健康对照）。在本研究中，我们发现 COMT rs4680 多态性与 LOAD 之间没有显著关联，即使在总样本中对年龄、性别和载脂蛋白 E（APOE）状态进行了统计调整，以及对 APOE 状态进行了分层后也是如此。我们的结果表明，COMT Val158Met 多态性在汉族人群 LOAD 的发展中可能不起主要作用。
