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Published on: August 18, 2015
Phosphodiesterase 4 D (PDE4D) gene polymorphisms and risk of ischemic stroke: A systematic review and meta-analysis
Manabesh Nath1, Priyanka Swarnkar1, Shubham Misra1,2
1Department of Neurology, All India Institute of Medical Sciences, New Delhi, 110029, India.
Insights
Phosphodiesterase 4 D (PDE4D) gene polymorphisms, specifically SNP45, SNP83, and SNP89, are linked to increased ischemic stroke risk in Asian populations. These genetic markers may serve as predictors for stroke occurrence, particularly in Asians.
Area of Science:
- Genetics
- Neurology
- Epidemiology
Background:
- Conflicting evidence exists regarding the association between Phosphodiesterase 4 D (PDE4D) gene polymorphism and ischemic stroke (IS) risk.
- This meta-analysis aims to clarify this relationship by pooling data from published epidemiological studies.
Approach:
- A comprehensive literature search was conducted across multiple databases up to December 2021.
- Pooled Odds Ratios (ORs) and 95% Confidence Intervals (CIs) were calculated under various genetic models (dominant, recessive, allelic).
- Subgroup analyses by ethnicity (Caucasian vs. Asian) and sensitivity analyses were performed to assess reliability and heterogeneity.
Key Points:
- The meta-analysis included 47 case-control studies with 20,644 IS cases and 23,201 controls.
- Significant associations were found between SNP45 (recessive model), SNP83 (allelic model), and SNP89 (dominant and recessive models) polymorphisms and IS risk, particularly in the Asian subgroup.
- No significant relationship was observed for SNP32, SNP41, SNP26, SNP56, and SNP87 polymorphisms with IS risk.
Conclusions:
- SNP45, SNP83, and SNP89 polymorphisms are associated with increased stroke susceptibility in Asians, but not Caucasians.
- Genotyping of these specific PDE4D polymorphisms may serve as a predictive tool for ischemic stroke occurrence, especially in Asian individuals.
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 22nd 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.
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