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Background Recent evidence has implicated the gene for phosphodiesterase 4D (PDE4D) as susceptibility gene for ischemic stroke (IS) in lcelandic population.However,there are few reports on the associations between PDE4D gene polymorphisms and IS in Chinese individuals.The present study aimed to investigate the possible association of genetic polymorphisms in PDE4D gene with IS in Henan Han population.Methods A total of 400 patients with IS and 400 matched controls were examined using a case-control design.Two single nucleotide polymorphism (SNPs) (rs918592 and rs2910829) in PDE4D gene were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.Odds ratios (OR) and 95％ confidence intervals (95％ Cl) were calculated to test the association between the genetic factors and IS.Genetic parameter and association studies were carried out with SPSS 16.0.Results Among the two SNPs tested,the rs918592 was significantly associated with IS (OR:1.351,95％ Cl:1.110-1.645),especially in male patients (OR:1.427,95％ Cl:1.105-1.844).Haplotype analysis showed that A-T was associated with an increased risk of the IS (OR:2.114,95％ Cl:2.005-2.230) while G-T was associated with decreased risk of IS (OR:0.419,95％ Cl:0.302-0.583).Protecting effect of haplotype G-T was also significant in males (OR:0.264,95％ Cl:0.162-0.431).Conclusions The present study demonstrated a strong association of rs918592 with IS.Haplotype A-T increased the risk of IS while haplotype G-T had a protective effect in Henan Hen population.The association was sex-dependent with male patients showing stronger effect.