Background and Objectives-Identification of STRK1 locus by the deCODE group followed by the discovery of phosphodiesterase 4D (PDE4D) gene in strong association with ischemic stroke patients has provided useful insights toward understanding the genetic etiology of the disease. In this study, we aimed at investigating the association between 3 polymorphisms of the PDE4D gene and ischemic stroke in the Pakistani population. Methods-Three polymorphisms in PDE4D gene were analyzed in 200 patients of ischemic stroke and 250 controls of Pakistani origin using polymerase chain reaction-restriction fragment length polymorphism method. Data were coded and entered in SPSS Windows (version 12.0). Odds ratios and 95% CIs were calculated using multivariate logistic regression analysis. Although the past 3 decades have seen a decline in the incidence of the disease in the Western population, 1 the burden of the disease in South Asian countries (India, Pakistan, Bangladesh, and Sirilanka) has inclined and is expected to rise. 3 Several epidemiologic studies in families and in twins have indicated a distinctive genetic component predisposing to stroke. 4 However, identification of these factors remained elusive until the discovery of STRK1 locus by deCODE group, 5 followed by association of the phosphodiesterase 4D (PDE4D) with ischemic stroke in the Icelandic population. 6 In this study, we investigated the association between 3 polymorphisms of the PDE4D gene and ischemic stroke in the Pakistani population. Results-Marker MethodsThe study was conducted at the Liaqat National Hospital and Aga Khan University Hospital Karachi in 2001 to 2002. The study population consisted of 200 patients of ischemic stroke and 250 controls. Ischemic stroke was defined as a sudden loss of global or focal cerebral function persisting for Ͼ24 hours with corresponding infarction on brain imaging with a probable vascular cause. All patients underwent a complete neurological examination. Data were collected with the help of a pretested and coded data extraction sheet. Controls were free of stroke and were from local population sharing the same environment. The study was approved by the ethics committee of both hospitals.An individual was classified as having arterial hypertension with a previous diagnosis of hypertension or if systolic or diastolic blood pressure was Ͼ140 mm Hg or Ͼ90 mm Hg, respectively, on Ն2 different occasions. Subjects were classified as having diabetes mellitus if he or she already had the diagnosis of diabetes mellitus or if his or her fasting plasma glucose was Ͼ126 mg/dL. Ischemic heart disease was established on past medical history, review of ECGs, and other relevant clinical information. Sample size of 200 cases and 250 controls based on allele frequencies was calculated for a power of 80% using the software Quanto. 7 Laboratory Measurement and TechniquesA total of 10 mL of venous blood was collected in an EDTA tube and plain tubes separately for DNA extraction from white blood cells and serum analysis. DNA was extracted...

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