Blood Clusterin Levels, Rs9331888Polymorphism And The Risk Of Alzheimer’s Disease

Objective:To define the relationship and the underlying mechanisms between Blood clusterin levels, rs9331888Polymorphism and the Risk of late-onset Alzheimer’s disease (LOAD) in a Chinese Han population.Methods:104LOAD patients and104healthy subjects matched for sex and age were recruited for the study. A single nucleotide polymorphisms (rs9331888) of CLU and ApoE gene were detected using Matrix-Assisted Laser Desorption Ioniziation-Mass Spectrometry (MALDI-MS) and multiplex amplification mutation system PCR (Multi-ARMS). Plasma clusterin concentration was tested using the Human Clusterin ELISA (BioVendor, Heidelberg, Germany). Clusterin mRNA levels of PBMC were measured by Real-time Quantitative RT-PCR. The clusterin mRNA and plasma protein levels of AD cases to that of healthy subjects were compared using the Student’s t-test, and the genotype effects within each group were tested using one-way analysis of variance (ANOVA) followed by Bonferroni. The correlations between mRNA, protein levels and MMSE score were performed with Pearson’s coefficient.Result:The results revealed that there were significant differences in genotype (P=0.001) and allele (P＜0.001) frequencies of the SNP rs9331888between AD patients and controls. The G allele occurred at a greater frequency in patients versus controls (OR=2.17;95%CI=1.45-3.23;p<0.001). The presence of the ApoE ε4allele was associated with an increased risk of LOAD (P=0.012). Clusterin mRNA and plasma clusterin levels in AD patients were significantly higher than controls (mean±SD:0.537±0.149versus0.486±0.122,p=0.007;167.01±13.40μg/ml versus162.74±10.03μg/ml,p=0.01, respectively). In both groups, we found that expression of clusterin mRNA and plasma clusterin levels with the GG genotype as well as CG genotype were significantly lower than that with CC genotype (p<0.001). A significant negative correlation between plasma clusterin levels and global cognition (MMSE score, mean±SD:5.79±4.39) in AD patients (r=-0.110, p<0.01). A negative correlation between mRNA levels and MMSE score was also observed (r=-0.576, p<0.01).Conclusions:Blood clusterin levels were significantly elevated in AD patients. The rs9331888AD-risk variant was associated with low clusterin mRNA and protein levels in an allele-dose dependent manner in both groups (p<0.001). The rs9331888AD-risk variant may be associated with low blood clusterin levels.