The Association of MME microRNA Binding Site Polymorphism with the Risk of Late Onset Alzheimer's Disease in Northern Han Chinese

作者：Liu, Chun-Xia; Tan, Lin; Sun, Fu-Rong; Zhang, Wei; Miao, Dan; Tan, Meng-Shan; Wan, Yu; Tan, Chen-Chen; Yu, Jin-Tai; Tan, Lan

来源：Current Neurovascular Research, 2017, 14(2): 90-95.

DOI：10.2174/1567202614666170313110301

• Neprilysin
• MME
• polymorphism
• rs6665
• late onset alzheimer's disease

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.

• 出版日期2017
• 单位青岛市市立医院; 青岛大学