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

Abstract

Purpose: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

Keywords: Alzheimer disease; Cyclooxygenase-2; Meta-analysis; PTGS-2; Polymorphism.