Association between clusterin gene polymorphism rs11136000 and late-onset Alzheimer's disease susceptibility: A review and meta-analysis of case-control studies

The present study aimed to evaluate the association between rs11136000 in clusterin (CLU) and late-onset Alzheimer's disease (LOAD) by meta-analysis. Several databases including PubMed, EMbase, CBMdisc and CMCC were searched for relevant case-control studies based on defined selection criteria. Odds ratios (OR) and 95% confidence interval (CI) of the rs11136000 genotype and allele distribution were analyzed with RevMan and Stata software. The control population and heterogeneity between populations were examined in the selected studies using the Hardy-Weinberg equilibrium. Overall OR among the frequencies of the genotype and allele in both patients with AD and controls was estimated using fixed or random effect models. The summary of the OR and 95% CI were then analyzed to obtain the effects across the studies. Publication bias was examined using a funnel plot, Egger's test and Begg's test, and a Fail-safe Number (N(fs)). A total of 20 reports were used. The summary OR for studies in the Caucasian population with a frequency of TT+TC/CC genotype and T/C allele at rs11136000 locus in CLU were 0.79 (95% CI, 0.73–0.86; P<0.00001) and 0.87 (95% CI, 0.85–0.90; P<0.00001). The summary OR for the studies conducted in the Asian population were 0.90 (95% CI, 0.81–0.99; P=0.04) and 0.87 (95% CI, 0.81–0.93; P<0.0001). The summary OR in other mixed ethnic groups with regards to the frequency of T/C allele was 0.82 (95% CI, 0.68–0.99; P=0.04). These results demonstrated the presence of a statistically significant difference in LOAD susceptibility between individuals with the T allele CLU rs11136000 polymorphism and those without. The studies conducted in populations of African descent or Hispanics showed no statistically significant difference. Negligible publication bias was present, with N(fs) being 750.604. In summary, polymorphism rs11136000 in the CLU gene may contribute to susceptibility to LOAD, and the presence of the T allele may reduce the risk of LOAD in Caucasian and Asian populations. However, no definitive association was found between the presence of the CLU rs11136000 polymorphism and LOAD in populations of African or Hispanic descent.