Impact of the PDE4D gene polymorphism and additional SNP-SNP and gene-smoking interaction on ischemic stroke risk in Chinese Han population.
AIMS
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.
['Wang|Xianxiang|X|', 'Sun|Zhongwu|Z|', 'Zhang|Yiquan|Y|', 'Tian|Xuefeng|X|', 'Li|Qingxin|Q|', 'Luo|Jing|J|']
D000368:Aged D044466:Asians D002545:Brain Ischemia D016022:Case-Control Studies D002681:China D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 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 D020521:Stroke
PDE4D polymorphisms interaction Ischemic stroke smoking