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.