Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No.5 Donghai Middle Road, Qingdao, China.
J Neuroinflammation. 2011 Oct 11;8:136. doi: 10.1186/1742-2094-8-136.
Toll-like receptor 2 (TLR2) represents a reasonable functional and positional candidate gene for Alzheimer's disease (AD) as it is located under the linkage region of AD on chromosome 4q, and functionally is involved in the microglia-mediated inflammatory response and amyloid-β clearance. The -196 to -174 del polymorphism affects the TLR2 gene and alters its promoter activity.
We recruited 800 unrelated Northern Han Chinese individuals comprising 400 late-onset AD (LOAD) patients and 400 healthy controls matched for gender and age. The -196 to -174 del polymorphism in the TLR2 gene was genotyped using the polymerase chain reaction (PCR) method.
There were significant differences in genotype (P = 0.026) and allele (P = 0.009) frequencies of the -196 to -174 del polymorphism between LOAD patients and controls. The del allele was associated with an increased risk of LOAD (OR = 1.31, 95% CI = 1.07-1.60, Power = 84.9%). When these data were stratified by apolipoprotein E (ApoE) ε4 status, the observed association was confined to ApoE ε4 non-carriers. Logistic regression analysis suggested an association of LOAD with the polymorphism in a recessive model (OR = 1.64, 95% CI = 1.13-2.39, Bonferroni corrected P = 0.03).
Our data suggest that the -196 to -174 del/del genotype of TLR2 may increase risk of LOAD in a Northern Han Chinese population.
Toll 样受体 2（TLR2）作为阿尔茨海默病（AD）的一个合理的功能和位置候选基因，位于 AD 染色体 4q 的连锁区域内，在功能上参与小胶质细胞介导的炎症反应和淀粉样β清除。-196 至-174 缺失多态性影响 TLR2 基因并改变其启动子活性。
我们招募了 800 名无血缘关系的北方汉族个体，包括 400 名迟发性 AD（LOAD）患者和 400 名性别和年龄匹配的健康对照者。使用聚合酶链反应（PCR）方法对 TLR2 基因的-196 至-174 缺失多态性进行基因分型。
LOAD 患者与对照组之间，TLR2 基因-196 至-174 缺失多态性的基因型（P=0.026）和等位基因（P=0.009）频率存在显著差异。缺失等位基因与 LOAD 的发病风险增加相关（OR=1.31，95%CI=1.07-1.60，Power=84.9%）。当根据载脂蛋白 E（ApoE）ε4 状态对这些数据进行分层时，观察到的相关性仅限于 ApoE ε4 非携带者。Logistic 回归分析表明，LOAD 与多态性在隐性模型中存在关联（OR=1.64，95%CI=1.13-2.39，Bonferroni 校正 P=0.03）。
我们的数据表明，TLR2 的-196 至-174 缺失/缺失基因型可能会增加北方汉族人群 LOAD 的发病风险。
