Phosphodiesterase 4D polymorphisms associate with the short-term outcome in ischemic stroke

Abstract

It has been demonstrated that phosphodiesterase 4D (PDE4D) genetic polymorphism is associated with ischemic stroke. However, the association between PDE4D gene and prognosis after ischemic stroke remains unknown. We consecutively enrolled ischemic stroke patients admitted to Beijing Tiantan Hospital from October 2009 to December 2013. Clinical, laboratory and imaging data upon admission were collected. All patients were followed up 3 months after stroke onset. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the associations of genetic polymorphisms with 3-month outcome after ischemic stroke and different subtypes, under various genetic models. A total of 1447 patients were enrolled, and 3-month follow-up data were obtained from 1388 (95.92%). Multivariate regression analysis showed that SNP87 of PDE4D gene was associated with increased risk of unfavorable outcome after total ischemic stroke (OR = 1.47, 95%CI 1.12–1.93), as well as stroke due to large-artery atherosclerosis (OR = 1.49, 95%CI 1.04–2.11) and small-artery occlusion (OR = 1.76, 95%CI 1.05–2.96) under a recessive model. No association between SNP83 genotype and poor outcome was found. Overall, this study demonstrated that the TT genotype of SNP87 in PDE4D was associated with increased risk of poor outcome after total ischemic stroke, large-artery atherosclerosis and small-artery occlusion, in a Chinese population.

Association of GWAS‐susceptibility loci with ischemic stroke recurrence in a Han Chinese population

“…Subsequently, several studies have demonstrated a positive association between IS and rs966221 in PDE4D , 16,17 and a meta‐analysis has confirmed this association 18 . Recently, Song et al 19 . reported that rs966221 within PDE4D was associated with increased risk of a poor outcome 3 months post‐stroke.…”

MiR-139-5p has an antidepressant-like effect by targeting phosphodiesterase 4D to activate the cAMP/PKA/CREB signaling pathway

“…The PDE4 gene family consists of four subtypes (PDE4A-D) and more than 20 splice variants (18). PDE4D is located in chromosome 5q12 and encodes cAMP-specific 3',5'-cyclic phosphodiesterase 4D (19). PDE4D mRNA is mainly expressed in the emetic center of the mouse hippocampus (such as the nucleus tractus solitarius), but it is upregulated after CUMS mode (20).…”

Thromboxane A synthase 1 gene expression and promotor haplotypes are associated with risk of large artery‐atherosclerosis stroke in Iranian population

“…Third, although the association of variants with TBXAS1 transcripts level in platelets was demonstrated, the protein level of TBXAS1 was not measured in this study; moreover, testing the protein level of TBXAS1 in platelets and investigating the SNPs effect on promoter activity by luciferase assay can reveal more details about the SNPs effect on TBXAS1 promoter activity. Finally, undoubtedly IS is the complex multifactorial disorder believed to be the result of an interaction between the genetic background of an individual and various environmental factors . Although we have identified the association between TBXAS1 SNPs and their haplotypes and the risk of LAA stroke, many environmental and genetic factors and their interactions remained unmeasured.…”