Common Polymorphisms in the GSK3β Gene May Contribute to the Pathogenesis of Alzheimer Disease: A Meta-Analysis

Objective: Although it is well known that GSK3 participates in the proliferation and survival of various tumor cells, its role in diseases of the central nervous system has been sparsely documented. In the past few years, studies regarding the relationship between GSK3 rs334558 T>C and rs6438552 C>T polymorphisms and Alzheimer disease (AD) risk have yielded contradictory results. As such, this meta-analysis seeks to satisfy the need to further investigate this relationship. Methods: In this research, published studies regarding the association of GSK3 rs6438552 and rs334558 mutation with AD risk was systematically assessed. Studies were retrieved from MEDLINE, Science Citation Index, the Cochrane Library, PubMed, Embase, CINAHL, Current Contents Index, Chinese Biomedical, Chinese Journal Full-Text, and Weipu Journal. Pooled odds ratios and 95% confidence intervals were calculated for allele contrast and homozygous, heterozygous, dominant, and recessive genetic model comparisons. Results: It was found that GSK3 rs334558 T>C and rs6438552 C>T polymorphisms were correlated with susceptibility to AD under 4 genetic models (all P < .05). In country-stratified subgroups, the results showed increased risk of developing AD in rs334558 T>C polymorphism among Chinese and Spain populations in majority groups. GSK3 rs6438552 C>T polymorphism was correlated with increased the risk of developing AD only in Australian populations. Conclusion: Our findings suggest that there exists a significant association between GSK3 rs334558 T>C polymorphism and increased susceptibility of AD. Moreover, future updated studies with stratified case-control population are warranted for validation studies.