title: Impact of the PDE4D gene polymorphism and additional SNP-SNP and gene-smoking interaction on ischemic stroke risk in Chinese Han population.
abstract: OBJECTIVE
  To investigate the association between phosphodiesterase 4D gene (PDE4D) gene single nucleotide polymorphisms (SNPs) and ischemic stroke (IS) risk, and impact of additional SNP- SNP and gene- smoking interaction on IS risk in Chinese population.
  
  
  METHODS
  A total of 1228 subjects (666 males, 562 females) were selected, including 610 IS patients and 618 control subjects. Logistic regression model was used to examine the association between SNPs in PDE4D gene and IS risk. Generalized multifactor dimensionality reduction (GMDR) was employed to analyze the SNP- SNP and gene- smoking interaction.
  
  
  RESULTS
  IS risks were significantly higher in carriers of A allele of rs12188950 polymorphism than those with GG genotype (GA + AA vs. GG), adjusted OR (95%CI) = 1.61 (1.26-2.19), and also significantly higher in carriers of T allele of rs966221 polymorphism than those with CC (CT + TT vs. CC), adjusted OR (95%CI) = 1.82 (1.39-2.23). We found that there was a significant SNP- SNP interaction between rs966221 and rs12188950. Subjects with CT or TT of rs966221 and GA or AA of rs12188950 genotype have the highest IS risk, compared to subjects with CC of rs966221 and GG of rs12188950 genotype, OR (95%CI) was 3.52 (2.68-4.69). We also found a significant gene-environment interaction between rs966221 and smoking. Smokers with CT or TT of rs966221 genotype have the highest IS risk, compared to never smokers with CC of rs966221 genotype, OR (95%CI) was 3.97 (2.25-5.71).
  
  
  CONCLUSIONS
  Our results support an important association of rs966221 and rs12188950 minor allele and its interaction with increased risk of IS risk, and additional interaction between rs966221 and smoking.
authors.affiliation: a Department of Neurosurgery , The Affiliated Hospital of Anhui Medical University , Hefei , China.
authors.forename: Xianxiang
authors.initials: X
authors.lastname: Wang
authors.affiliation: b Department of Neurology , The Affiliated Hospital of Anhui Medical University , Hefei , China.
authors.forename: Zhongwu
authors.initials: Z
authors.lastname: Sun
authors.affiliation: a Department of Neurosurgery , The Affiliated Hospital of Anhui Medical University , Hefei , China.
authors.forename: Yiquan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: a Department of Neurosurgery , The Affiliated Hospital of Anhui Medical University , Hefei , China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Tian
authors.affiliation: a Department of Neurosurgery , The Affiliated Hospital of Anhui Medical University , Hefei , China.
authors.forename: Qingxin
authors.initials: Q
authors.lastname: Li
authors.affiliation: a Department of Neurosurgery , The Affiliated Hospital of Anhui Medical University , Hefei , China.
authors.forename: Jing
authors.initials: J
authors.lastname: Luo
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics; D002545:Brain Ischemia / Q000150:complications / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006579:Heterozygote; D006801:Humans; D016015:Logistic Models; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000235:genetics*; D020521:Stroke / Q000150:complications / Q000235:genetics*
chemical_list: D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C517376:PDE4D protein, human
keywords: Ischemic stroke; PDE4D; interaction; polymorphisms; smoking