Phosphodiesterase 4 D (PDE4D) gene polymorphisms and risk of ischemic stroke: A systematic review and meta-analysis

Background and purpose Studies on the relationship between Phosphodiesterase 4 D (PDE4D) gene polymorphism with the risk of ischemic stroke (IS) have shown discordant results. The present meta-analysis was aimed to clarify the relationship between PDE4D gene polymorphism with the risk of IS by estimating pooled analysis of published epidemiological studies. Methods A comprehensive literature search for all the published articles was performed in various electronic databases, including PubMed, EMbase, Cochrane Library, Trip Database, Worldwide Science, CINAHL, and Google Scholar up to 22 nd December 2021. Pooled Odds ratios (ORs) with 95% Confidence Intervals (CIs) under dominant, recessive, and allelic models were calculated. Subgroup analysis based on ethnicity (Caucasian vs. Asian) was performed to examine the reliability of these findings. Sensitivity analysis was also performed to detect the heterogeneity between studies. Finally, Begg’s funnel plot was used to assess the potential for publication bias. Results In our meta-analysis, we identified a total of 47 case–control studies with 20,644 ischemic stroke (IS) cases and 23,201 control subjects, including 17 studies of Caucasian descent and 30 studies of Asian descent. Our findings suggest that there was a significant relationship between SNP45 gene polymorphism and risk of IS (Recessive model: OR = 2.06, 95% CI 1.31–3.23), SNP83 overall (allelic model: OR = 1.22, 95% CI 1.04–1.42), Asian (allelic model: OR = 1.20, 95% CI 1.05–1.37), and SNP89 Asian (Dominant model: OR = 1.43, 95% CI 1.29–1.59, recessive model: OR = 1.42, 95% CI 1.28–1.58) respectively. However, no significant relationship was found between SNP32, SNP41, SNP26, SNP56, and SNP87 gene polymorphisms and risk of IS. Conclusion Findings of this meta-analysis conclude that SNP45, SNP83, and SNP89 polymorphism could be capable of increasing stroke susceptibility in Asians but not in the Caucasian population. Genotyping of SNP 45, 83, 89 polymorphisms may be used as a predictor for the occurrence of IS.