de Mendonça E, Salazar Alcalá E, Fernández-Mestre M
Laboratorio de Fisiopatología, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela.
Laboratorio de Fisiopatología, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela.
Neurologia. 2016 Oct;31(8):535-42. doi: 10.1016/j.nrl.2014.10.012. Epub 2014 Dec 24.
Several studies have reported increased oxidation of lipids, proteins and DNA in the brains of patients with Alzheimer disease (AD). Moreover, these patients display differences in the activity and polymorphisms of the genes encoding the enzymes GST (T1, M1) and MnSOD. For these reasons, we designed a study of the variability in GSTT1, GSTM1, and MnSOD genes in healthy and AD groups from a Venezuelan population.
We included 179 unrelated Venezuelan subjects classified as either AD patients (n=79) or healthy individuals (n=100). Presence or absence of the GSTT1/GSTM1 genes was determined using PCR-SSP, and polymorphisms of MnSOD and APOE genes were identified with PCR-RFLP.
The genotype GSTT1+/GSTM1- seems to favour development of AD (OR=2.06, P=.01). The risk level is higher when it is combined with the ɛ4 allele of the APOE gene: GSTT1+/GSTM1-/ɛ3ɛ4 (OR=3.07, P=.05), GSTT1+/GSTM1-/ɛ4ɛ4 (OR=5.52, P=.02). The Ala-9Val polymorphism does not appear to be related to AD. However, the presence of the Ala/Ala genotype increases the risk provided by the ɛ4 allele of the APOE gene: AlaAla/ɛ3ɛ4 (OR=3.47, P=.03), AlaAla/ɛ4ɛ4 (OR=6.3, P=.01).
The results support the hypothesis that impaired mitochondrial function and increased oxidative damage are involved in the pathogenesis of AD. It is important to study other genes related to oxidative stress and antioxidant pathways which could be involved in susceptibility to AD.
多项研究报告称，阿尔茨海默病（AD）患者大脑中脂质、蛋白质和DNA的氧化增加。此外，这些患者在编码谷胱甘肽S-转移酶（GST，T1、M1）和锰超氧化物歧化酶（MnSOD）的酶的活性和基因多态性方面存在差异。基于这些原因，我们设计了一项研究，以探讨委内瑞拉人群中健康组和AD组GSTT1、GSTM1和MnSOD基因的变异性。
我们纳入了179名无亲缘关系的委内瑞拉受试者，分为AD患者（n = 79）或健康个体（n = 100）。使用聚合酶链反应-序列特异性引物（PCR-SSP）确定GSTT1/GSTM1基因的有无，并通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）鉴定MnSOD和载脂蛋白E（APOE）基因的多态性。
基因型GSTT1+/GSTM1-似乎有利于AD的发展（比值比[OR]=2.06，P = 0.01）。当它与APOE基因的ɛ4等位基因结合时，风险水平更高：GSTT1+/GSTM1-/ɛ3ɛ4（OR = 3.07，P = 0.05），GSTT1+/GSTM1-/ɛ4ɛ4（OR = 5.52，P = 0.02）。丙氨酸-9缬氨酸多态性似乎与AD无关。然而，丙氨酸/丙氨酸基因型的存在增加了APOE基因ɛ4等位基因带来的风险：丙氨酸丙氨酸/ɛ3ɛ4（OR = 3.47，P = 0.03），丙氨酸丙氨酸/ɛ4ɛ4（OR = 6.3，P = 0.01）。
结果支持线粒体功能受损和氧化损伤增加参与AD发病机制的假说。研究其他与氧化应激和抗氧化途径相关的基因很重要，这些基因可能与AD易感性有关。
