title: Strong Association of Lipid Metabolism Related MicroRNA Binding Sites Polymorphisms with the Risk of Late Onset Alzheimer's Disease.
abstract: Although altered lipid metabolism has been extensively implicated in the pathogenesis of late onset Alzheimer's disease (LOAD) through cell biological and epidemiological studies, genetic studies linking lipid metabolism and LOAD are still not well understood. MicroRNAs (miRNAs) exert posttranscriptional down-regulation and their target sequence on the 3' untranslated regions (3'UTR) may be altered by single nucleotide polymorphisms (SNPs). We therefore explore whether the six loci in Clusterin gene (CLU) (rs9331949), Lipoprotein lipase gene (LPL) (rs1059507, rs3200218, rs3208305, rs3735964) and Low-density lipoprotein receptor related protein 6 (LRP6) (rs2160525) could modulate LOAD risk through the alteration of miRNA binding sites. We performed a case-control study of 2338 unrelated subjects (984 cases and 1354 age- and gender-matched controls) in the Northern Han Chinese. We found that the minor C allele in rs9331949 significantly increased the risk of LOAD (P<0.001, OR=1.31, 95% CI=1.14-1.51), even after adjusting for multiple testing. Logistic analysis identified the rs9331949 polymorphism was still strongly associated with LOAD, even in Apolipoprotein E (APOE) ε4 allele noncarrier subgroups. However, the other five loci were not significantly associated with LOAD after Bonferroni adjustment. In conclusion, we have identified that the locus (rs9331949) located in the binding site of 3' UTR of CLU has a strong association with LOAD rather than loci in LPL and LRP6. However, additional independent replication is required for further validation.
authors.forename: Lin
authors.initials: L
authors.lastname: Tan
authors.forename: Ang
authors.initials: A
authors.lastname: Xing
authors.forename: Da-Long
authors.initials: DL
authors.lastname: Zhao
authors.forename: Fu-Rong
authors.initials: FR
authors.lastname: Sun
authors.forename: Meng-Shan
authors.initials: MS
authors.lastname: Tan
authors.forename: Yu
authors.initials: Y
authors.lastname: Wan
authors.forename: Chen-Chen
authors.initials: CC
authors.lastname: Tan
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Dan
authors.initials: D
authors.lastname: Miao
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: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012306:Risk
chemical_list: D035683:MicroRNAs
keywords: Alzheimer's disease; association study; microRNA; polymorphism