Association of phosphodiesterase 4D gene with ischemic stroke in a Pakistani population.
OBJECTIVE
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.


CONCLUSIONS
The association of PDE4D variation with ischemic stroke extends to the Pakistani population and supports a role for phosphodiesterases in stroke pathogenesis.
Saleheen
Danish
D
Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan. danishsaleheen@yahoo.com
Bukhari
Shabbar
S
Haider
Shajjia Razi
SR
Nazir
Aisha
A
Khanum
Shaheen
S
Shafqat
Saad
S
Anis
M Kashif
MK
Frossard
Philippe
P
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000235:genetics*; D000368:Aged; D000483:Alleles; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005828:Genetics, Population; D005838:Genotype; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D015999:Multivariate Analysis; D016017:Odds Ratio; D010154:Pakistan; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors; D020521:Stroke / Q000201:enzymology* / Q000235:genetics*
D017931:DNA Primers; D005819:Genetic Markers; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C517376:PDE4D protein, human