Key result
PDE4D gene variants are linked to over fivefold higher ischemic stroke risk.
Why the study?
An association between the phosphodiesterase 4D (PDE4D) gene and risk of ischaemic stroke had been suggested but required further investigation and confirmation.
Is the phosphodiesterase 4D (PDE4D) gene associated with an increased risk of ischaemic stroke?
Case-Control (n=315)
Is the phosphodiesterase 4D (PDE4D) gene associated with an increased risk of ischaemic stroke?
The PDE4D gene is significantly associated with ischaemic stroke, suggesting it plays a key role in its pathogenesis, though the specific causal alleles remain unclear due to linkage disequilibrium.
Answers are grounded in this paper and cite their sources.
PDE4D variants may increase ischaemic stroke risk; hypothesis-generating and requires replication before clinical consideration.
BACKGROUND: An association between the phosphodiesterase 4D (PDE4D) gene and risk of ischaemic stroke in an Icelandic population has been suggested by the deCODE group. METHODS: A case-control study of 151 hospitalised patients with first-ever ischaemic stroke and 164 randomly selected age-matched and sex-matched community controls was conducted. PDE4D genotypes for the six single-nucleotide polymorphisms (SNPs) previously reported to be independently associated with stroke were determined, common haplotypes were inferred using the expectation-maximisation algorithm, and SNP and haplotype associations with stroke were examined. A meta-analysis of published studies examining the association between PDE4D and stroke was also carried out. RESULTS: Our study of Australian patients with stroke showed an independent association between ischaemic stroke and PDE4D SNP 89 (CC: odds ratio (OR) 5.55, 95% confidence interval (CI) 1.02 to 30.19; CA: OR 1.68, 95% CI 0.96 to 2.96; AA: OR 1 (reference)), SNP 87 (CC: OR 2.13, 95% CI 1.08 to 4.20; TC: OR 1.64, 95% CI 0.89 to 3.00; TT: OR 1 (reference)) and SNP 83 (TT: OR 2.16, 95% CI 1.08 to 4.32; TC: OR 1.37, 95% CI 0.77 to 2.43; CC: OR 1 (reference)), and between ischaemic stroke and PDE4D haplotypes at SNP 89-87-83 (A-C-C: OR 2.13, 95% CI 1.15 to 3.96; C-C-T: OR 2.25, 95% CI 1.29 to 3.92), but no association between ischaemic stroke and PDE4D SNP 56, SNP 45 or SNP 41, or with PDE4D haplotypes at SNP 56-45-41. A meta-analysis of nine case-control studies (including our current results) of 3808 stroke cases and 4377 controls confirmed a significant association between stroke and PDE SNP 87 (pooled p = 0.002), SNP 83 (0.003) and SNP 41 (0.003). However, there was statistical heterogeneity (p < 0.1) among the studies in the direction of association for each of the individual SNPs tested. CONCLUSIONS: Our results and the pooled analyses from all the studies indicate a strong association between PDE4D and ischaemic stroke. This strengthens the evidence that PDE4D plays a key part in the pathogenesis of ischaemic stroke. Heterogeneity among the studies in the direction of association between individual SNPs and stroke suggests that the SNPs tested are in linkage disequilibrium with the causal allele(s).
No takes yet. Share an insight, caveat, or question.
Janelle M. Staton (2006) conducted a case-control in Ischaemic stroke (n=315). PDE4D gene SNPs (SNP 89, 87, 83) vs. Reference genotypes was evaluated on Ischaemic stroke (OR 5.55, 95% CI 1.02 to 30.19, p=0.002). PDE4D gene variants, particularly SNP 89 (OR 5.55; 95% CI 1.02-30.19), SNP 87, and SNP 83, were significantly associated with an increased risk of ischaemic stroke.
Synapse has enriched 10 related papers. Consider them for comparative context: