title: Association of the phosphodiesterase 4D (PDE4D) gene and cardioembolic stroke in an Australian cohort.
abstract: BACKGROUND
  Large-scale epidemiological studies support an important role for susceptibility genes in the pathogenesis of ischemic stroke, with phosphodiesterase 4D identified as the first gene predisposing to ischemic stroke. Several single nucleotide polymorphisms within the phosphodiesterase 4D gene have been implicated in the pathogenesis of stroke. Aim Undertake a multivariate analysis of six single nucleotide polymorphisms within the phosphodiesterase 4D gene in a previously defined Australian stroke cohort, to determine whether these single nucleotide polymorphisms have an association with ischemic stroke.
  
  
  METHODS
  This case-control study was performed using an existing genetic database of 180 ischemic stroke patients and 301 community controls, evaluated previously for cerebrovascular risk factors (hypertension, hypercholesterolemia, diabetes, paroxysmal atrial fibrillation, smoking and history of stroke in a first-degree relative). Based on previously reported associations with large vessel disease, ischemic stroke, cardioembolic stroke or a mixture of these, six single nucleotide polymorphisms in the phosphodiesterase 4D gene were selected for study, these being single nucleotide polymorphisms 13, 19, rs152312, 45, 83 and 87, based on previously utilized DeCODE nomenclature. Single nucleotide polymorphisms were genotyped using a sequence-specific polymerase chain reaction method and gel electrophoresis. Logistic regression was undertaken to determine the relevance of each polymorphism to stroke. Further analysis was undertaken to determine the risk of stroke following stratification for stroke sub-type and etiology.
  
  
  RESULTS
  Significant odds ratios were found to be associated with cardioembolic strokes in two single nucleotide polymorphisms: rs152312 and SNP 45 (P < 0 · 05).
  
  
  CONCLUSIONS
  Our findings demonstrated an association between cardioembolic stroke and phosphodiesterase 4D single nucleotide polymorphisms rs152312 and 45. No significant association was found for the other four single nucleotide polymorphisms investigated within the phosphodiesterase 4D gene. We propose that the results from this Australian population support the concept that a large prospective international study is required to investigate the role of phosphodiesterase 4D in the cardiogenic cause of ischemic stroke.
authors: Stroke Research Programme, School of Medicine, University of Adelaide, The Queen Elizabeth Hospital campus, South Australia 5011, Australia.
authors: Austin G
authors: AG
authors: Milton
authors: Verna M
authors: VM
authors: Aykanat
authors: M Anne
authors: MA
authors: Hamilton-Bruce
authors: Mark
authors: M
authors: Nezic
authors: Jim
authors: J
authors: Jannes
authors: Simon A
authors: SA
authors: Koblar
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001315:Australia / Q000453:epidemiology; D002545:Brain Ischemia / Q000453:epidemiology / Q000235:genetics; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000235:genetics*; D004247:DNA / Q000235:genetics; D017931:DNA Primers; D004617:Embolism / Q000150:complications* / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics*
chemical_list: D017931:DNA Primers; D004247:DNA; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4