Cyclooxygenase-2 gene polymorphisms and risk of Alzheimer's disease: A meta-analysis

Cyclooxygenase-2 (COX-2) is one of the key enzymes in the synthesis of prostaglandins, and plays a pivotal role in inflammatory response. Recent studies have suggested cyclooxygenase-2 is involved in the pathogenesis of Alzheimer's disease (AD). However, the relationship between COX-2 gene polymorphisms (-765G>C rs20417, -1195A>G rs689466) and Alzheimer's disease risk is not conclusive. We conducted a meta-analysis to systematically examine and to clarify the association between the two SNPs and AD risk.

PubMed, EMBASE, Web of Science, Cochrane Library and CBMdisc were searched in July 2015 to identify eligible studies. Odds ratio (OR) and 95% confidence intervals (95% CI) were used to assess the strength of association.

A total of 7 case-control studies about COX-2 rs20417 polymorphisms and AD risk, and 3 studies about COX-2 rs689466 and AD risk were included in this meta-analysis. For rs20417 (-765G>C), there was a significant association between rs20417 and AD, and the risk for AD decreased in all gene models (C allele versus G allele: OR=0.570 CI 0.484-0.672; CC+GC versus GG: OR=0.568 CI 0.470-0.686; CC versus GC+GG: OR=0.357, CI 0.217-0.587; CC versus GG: OR=0.311, CI 0.189-0.514; GC versus GG: OR=0.613 CI 0.503-0.746).

C-allele of rs20417 (-765G>C) polymorphism was associated with reduced risk of AD, and might be a protective factor. Because of the limit sample and heterogeneity, the association between rs689466 polymorphism and AD risk should be treated with caution. To further confirm this relationship, larger-scale and better-designed studies should be conducted in the future.