Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, Shandong Province 266071, PR China.
Neurosci Lett. 2011 Feb 11;489(3):164-7. doi: 10.1016/j.neulet.2010.12.008. Epub 2010 Dec 14.
The amyloid beta protein (Aβ) deposits in the brains of patients with Alzheimer's disease (AD) are closely associated with innate immune responses that were assumed to play a pivotal role in the pathogenesis of AD. Toll-like receptor 2 (TLR2) is thought to contribute to Aβ clearance. Studies have reported the presence and functional implications of guanine-thymine (GT) repeat microsatellite polymorphisms in intron II of the human TLR2 gene. The present study evaluated the association of the microsatellite polymorphism and sporadic late-onset AD (LOAD) in the Han Chinese population. The numbers of (GT) repeats were counted in 137 AD patients and in 137 non-AD control subjects, using polymerase chain reaction and genescan analysis. The alleles were divided into three subclasses: (GT)16 or less as the S allele, (GT)17 to (GT)22 as the M allele, and (GT)23 or more as the L allele. Patients with AD had more S alleles (P<0.001; odds ratio (OR)=2.32; 95% confidence interval (CI)=1.57-3.42) and fewer L alleles (P=0.02; OR=0.66; 95% CI=0.46-0.93) than did healthy controls. Genotypes SS and SM were more common, whereas ML and SL were less common in patients with AD. In subgroup analyses, the genotypes including S alleles were associated with an increased risk of LOAD (OR=2.05, 95% CI=1.26-3.34), and this association was influenced by the presence of APOE ɛ4 alleles. This study demonstrates an association of microsatellite polymorphisms in intron II of the human TLR2 gene with risk for LOAD in Han Chinese.
淀粉样β蛋白(Aβ)在阿尔茨海默病(AD)患者的大脑中沉积,与先天免疫反应密切相关,后者被认为在 AD 的发病机制中起关键作用。Toll 样受体 2(TLR2)被认为有助于 Aβ的清除。研究报告了人类 TLR2 基因内含子 II 中鸟嘌呤-胸腺嘧啶(GT)重复微卫星多态性的存在及其功能意义。本研究评估了微卫星多态性与汉族人群散发性晚发性 AD(LOAD)的关联。使用聚合酶链反应和基因扫描分析,在 137 例 AD 患者和 137 例非 AD 对照中计数(GT)重复数。等位基因分为 3 个亚类:(GT)16 或以下为 S 等位基因,(GT)17 至(GT)22 为 M 等位基因,(GT)23 或更多为 L 等位基因。AD 患者的 S 等位基因(P<0.001;优势比(OR)=2.32;95%置信区间(CI)=1.57-3.42)较多,L 等位基因(P=0.02;OR=0.66;95%CI=0.46-0.93)较少。AD 患者的 SS 和 SM 基因型更为常见,而 ML 和 SL 基因型则较少。在亚组分析中,包含 S 等位基因的基因型与 LOAD 的风险增加相关(OR=2.05,95%CI=1.26-3.34),这种关联受 APOE ɛ4 等位基因的影响。本研究表明,人类 TLR2 基因内含子 II 中的微卫星多态性与汉族 LOAD 的风险相关。