Published Online
on September 15, 2005

A more recent version of this article appeared on October 1, 2005

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Submitted on April 23, 2005
Revised on June 3, 2005
Accepted on June 7, 2005

Association of Phosphodiesterase 4D Gene With Ischemic Stroke in a Pakistani Population

Danish Saleheen MBBS^*; Shabbar Bukhari MBBS; Shajjia Razi Haider MSc; Aisha Nazir MSc; Shaheen Khanum MSc; Saad Shafqat PhD; M. Kashif Anis MD; and Philippe Frossard PhD

From the Department of Biological and Biomedical Sciences (D.S., S.B., S.R.H., A.N., S.K., P.F.), Aga Khan University, Karachi, Pakistan; Section of Neurology (S.S.), Department of Medicine, Aga Khan University, Karachi, Pakistan; Liaquat National Hospital (M.K.A.), Karachi, Pakistan; and Section of Gastroenterology (M.K.A.), Department of Medicine, Aga Khan University, Karachi, Pakistan.

^* To whom correspondence should be addressed. E-mail: danishsaleheen{at}yahoo.com.

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.

Results--Marker SNP83(rs966221) was found significantly associated with ischemic stroke on univariate and multivariate analysis (P<0.005; odds ratio, 1.64 [1.13 to 2.40]). Haplotype analysis for markers in linkage disequilibrium failed to show any association with the disease.

Conclusion--The association of PDE4D variation with ischemic stroke extends to the Pakistani population and supports a role for phosphodiesterases in stroke pathogenesis.

Key words: genetics • risk factors • stroke, ischemic

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