Meta-analysis of homogeneous subgroups reveals association between PDE4D gene variants and ischemic stroke

Neuroepidemiology. 2011;36(4):213-22. doi: 10.1159/000327915. Epub 2011 Jun 16.

Abstract

Background: An Icelandic study showed a significant positive association between phosphodiesterase 4D (PDE4D) gene variants and stroke. However, subsequent studies reported conflicting results, possibly due to small sample sizes and the heterogeneity of the studies.

Method: We performed a meta-analysis on 6 SNPs of the PDE4D gene to investigate the association between this gene and ischemic stroke by integrating the results of previous studies, comprising 11,834 cases and 15,233 controls. A pooled genotypic odds ratio (OR) for each SNP was determined under 3 genetic models (i.e. dominant, recessive, and codominant) using both fixed- and random-effects models with consideration for heterogeneity and publication bias across studies.

Results: Among the SNPs included in this study, SNP56 (rs702553) showed the most significant association with ischemic stroke in a meta-analysis comprised of 7 homogenous studies. The overall OR of the TT genotype compared to the AA genotype was 1.29 (95% CI 1.03-1.61; p = 0.022). For SNP83 (rs966221), a protective effect of the ancestral allele T was observed only in Asian populations (ORTT 0.79, 95% CI 0.69-0.90; p = 0.0005). This meta-analysis revealed a significant association of PDE4D gene variants with the risk of ischemic stroke, and further investigations are warranted to evaluate possible ethnic-specific effects.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Brain Ischemia / genetics*
  • Cyclic Nucleotide Phosphodiesterases, Type 4 / genetics*
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Odds Ratio
  • Polymorphism, Single Nucleotide / genetics
  • Risk Factors
  • Stroke / genetics*

Substances

  • Cyclic Nucleotide Phosphodiesterases, Type 4