title: The Association of MME microRNA Binding Site Polymorphism with the Risk of Late Onset Alzheimer's Disease in Northern Han Chinese.
abstract: Although β-amyloid (Aβ) degradation has been normally implicated in the pathogenesis of late-onset Alzheimer's disease (LOAD) through cellular biological studies, the genetic studies linking Aβ degradation and LOAD are still scarce. Neprilysin (NEP), one of the most crucial Aβ-degrading enzymes in AD, is the metalloendopeptidase which particularly participates in the monomeric Aβ 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).
  
  
  
  To investigate the potential risk of common locus within NEP gene (MME) with LOAD in Northern Han Chinese population.
  
  
  
  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.
  
  
  
  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) ε4 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 ε4 status, rs6665 polymorphism was found to elevate the LOAD risk in ApoE ε4 carriers (P=0.002, OR=1.846, 95%CI=1.264-2.697).
  
  
  
  Our study firstly confirmed the association of MME miRNA binding site polymorphism with the risk of LOAD. However, the association results warrant further validation.
authors.affiliation: Department of Neurology, Heze Medical College, Heze, Shandong, China.
authors.forename: Chun-Xia
authors.initials: CX
authors.lastname: Liu
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Tan
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
authors.forename: Fu-Rong
authors.initials: FR
authors.lastname: Sun
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Miao
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
authors.forename: Meng-Shan
authors.initials: MS
authors.lastname: Tan
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wan
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
authors.forename: Chen-Chen
authors.initials: CC
authors.lastname: Tan
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
authors.forename: Jin-Tai
authors.initials: JT
authors.lastname: Yu
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No.5 Donghai Middle Road, Qingdao, Shandong Province 266071, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Tan
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000208:ethnology / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D044466:Asian People / Q000208:ethnology / Q000235:genetics; D001665:Binding Sites / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D035683:MicroRNAs / Q000235:genetics*; D015260:Neprilysin / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D001057:Apolipoproteins E; D035683:MicroRNAs; D015260:Neprilysin
keywords: MME; Neprilysin; late onset alzheimer’s disease; polymorphism; rs6665