The Association of MME microRNA Binding Site Polymorphism with the Risk of Late Onset Alzheimer's Disease in Northern Han Chinese
The Association of MME microRNA Binding Site Polymorphism with the Risk of Late Onset Alzheimer's Disease in Northern Han Chinese
复制标题
MME microRNA结合位点多态性与北方汉族晚发性阿尔茨海默病风险的关系
DOI：
10.2174/1567202614666170313110301
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发表时间：
2017-01-01
影响因子：
2.1
通讯作者：
Tan, Lan
中科院分区：
文献类型：
--
作者：
Liu, Chun-Xia;Tan, Lin;Tan, Lan
背景：虽然通过细胞生物学研究，β -淀粉样蛋白（A β）降解通常与晚发性阿尔茨海默病（LOAD）的发病机制有关，但将A β降解与LOAD联系起来的遗传学研究仍然很少。Neprilysin （NEP）是AD中最重要的A β降解酶之一，它是一种金属内肽酶，主要参与单体A β的降解。MicroRNAs （miRNAs）在3‘非翻译区（3’ UTR）发生转录后失调，其靶序列可能受到单核苷酸多态性（snp）的调控。目的：探讨北方汉族人群NEP基因共位点（MME）与LOAD的潜在风险。方法：筛选NEP基因（MME） 3′UTR位点（rs6665），筛选miRNA-187特异性调控的位点，并通过大型病例对照研究（984例LOAD患者和1354例健康对照）进一步探讨其与LOAD发病的关系。结果：荷重组rs6665基因型分布（P=0.003）和等位基因A/C分布（P=0.001）差异有统计学意义(优势比（OR) = 1.255, 95%可信区间(CI) = 1.102 ~ 1.429）。在调整年龄、性别和载脂蛋白（ApoE） epsilon 4状态后，rs6665的次要C等位基因在所有三种基因型模型中均与LOAD显著相关（显性：P= 0.003， OR= 1.291, 95% CI= 1.092 ~ 1.526；隐性：P= 0.030， OR= 1.425,95% CI= 1.035 ~ 1.961；加性：P= 0.001， OR= 1.249,95% CI= 1.093 ~ 1.427）。按ApoE e4状态分层后，发现rs6665多态性增加ApoE e4携带者的LOAD风险（P= 0.002， OR= 1.846, 95% CI= 1.264 ~ 2.697）。结论：我们的研究首次证实了MME miRNA结合位点多态性与LOAD风险的相关性。然而，该关联结果需要进一步验证。
Background: Although beta-amyloid (A beta) degradation has been normally implicated in the pathogenesis of late-onset Alzheimer's disease (LOAD) through cellular biological studies, the genetic studies linking A beta degradation and LOAD are still scarce. Neprilysin (NEP), one of the most crucial A beta-degrading enzymes in AD, is the metalloendopeptidase which particularly participates in the monomeric A beta species degradation. MicroRNAs (miRNAs) exert post-transcriptional dysregulation and their target sequence on the 3' untranslated regions (3' UTR) may be regulated by single nucleotide polymorphisms (SNPs).Objective: To investigate the potential risk of common locus within NEP gene (MME) with LOAD in Northern Han Chinese population.Method: We screened a locus (rs6665) in 3' UTR of NEP gene (MME) which sequence was specially regulated by miRNA-187, and further investigated its possible association with LOAD onset in a large case-control study (984 LOAD patients and 1354 healthy controls) in Northern Han Chinese.Results: The distribution of rs6665 genotype (P=0.003) and allele A/C (P=0.001) showed significant difference between LOAD and controls (Odds Ratio (OR) = 1.255, 95% Confidence Interval (CI) = 1.102-1.429). After adjusting for age, gender and Apolipoprotein (ApoE) epsilon 4 status, the minor C allele of rs6665 showed significant association with LOAD in all three genotypic models (Dominant: P= 0.003, OR= 1.291, 95% CI= 1.092-1.526; Recessive: P= 0.030, OR = 1.425,95% CI = 1.035-1.961; Additive: P= 0.001, OR= 1.249,95% CI= 1.093-1.427). After stratifying by ApoE e4 status, rs6665 polymorphism was found to elevate the LOAD risk in ApoE e4 carriers (P= 0.002, OR= 1.846, 95% CI= 1.264-2.697).Conclusion: Our study firstly confirmed the association of MME miRNA binding site polymorphism with the risk of LOAD. However, the association results warrant further validation.