Ischemic stroke risk in a southeastern Chinese population: Insights from 5-lipoxygenase activating protein and phosphodiesterase 4D single-nucleotide polymorphisms.
OBJECTIVE
Through a genome-wide linkage scan, an Icelandic genetic research group identified two new genes associated with ischemic stroke: the 5-lipoxygenase activating protein (ALOX5AP) gene and the phosphodiesterase 4D (PDE4D) gene. Because they regulate arterial inflammation and are closely related to atherosclerosis and plaque instability, these two mutated genes have become a research hotspot. The purpose of this study was to investigate the association between the risk of ischemic stroke and single-nucleotide polymorphisms (SNPs) in the ALOX5AP and PDE4D genes in a southeastern Chinese population.


METHODS
A total of 459 patients with stroke and 462 control individuals were recruited in the study. Four ALOX5AP SNPs (SG13S32, SG13S42, SG13S89, and SG13S114), and three PDE4D SNPs (SNP83, SNP87, and SNP45) were studied. SNP genotypes were determined by polymerase chain reaction amplification followed by allele-specific primer extension, with detection by matrix-assisted laser desorption/ionization time-of-flight. Data were coded and entered in SPSS Windows (version 16.0). Odds ratios and 95% confidence intervals were calculated using multivariate logistic regression analysis. Generalized multifactor dimensionality reduction (GMDR) analysis was applied to detect gene-gene interactions.


RESULTS
No statistically significant differences were found in the SNP genotype frequencies between cases and controls for the seven SNPs studied. GMDR analysis revealed no evidence of interactions between these seven polymorphic sites and an increased stroke risk. In addition, no association between different stroke types and the control group was detected. Results showed that only the ALOX5AP gene, and specifically the rs9551963 and rs4769060 genotypes, exhibited significantly different distributions between the stroke and control groups in female participants.


CONCLUSIONS
No association was found between SNPs of ALOX5AP or PDE4D and the risk of overall ischemic stroke in a southeastern Chinese population. Interactions between these two genes were not risk factors for cerebral infarction. In atherothrombotic and small-artery disease subtypes, none of the seven SNPs was associated with any stroke risk; however, the ALOX5AP gene might be related to ischemic stroke incidence in females.
Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, South Baixiang, 325000 Zhejiang, China.
Minjie
M
Shao
Department of Neurology, The Third Affiliated Hospital of Wenzhou Medical University, Ruian, Wangsong Road No. 108, 325200 Zhejiang, China; Department of Neurology, Affiliated Deyang Hospital of Chengdu University of Traditional Chinese Medicine, Deyang, Taishan North Road No. 173, 618000 Sichuan, China. Electronic address: yixingyang64@126.com.
Xingyang
X
Yi
Department of Neurology, The Third Affiliated Hospital of Wenzhou Medical University, Ruian, Wangsong Road No. 108, 325200 Zhejiang, China.
Lifen
L
Chi
Department of Neurology, The Third Affiliated Hospital of Wenzhou Medical University, Ruian, Wangsong Road No. 108, 325200 Zhejiang, China.
Jing
J
Lin
Department of Neurology, The Third Affiliated Hospital of Wenzhou Medical University, Ruian, Wangsong Road No. 108, 325200 Zhejiang, China.
Qiang
Q
Zhou
Department of Neurology, The Third Affiliated Hospital of Wenzhou Medical University, Ruian, Wangsong Road No. 108, 325200 Zhejiang, China.
Ruyue
R
Huang
D058927:5-Lipoxygenase-Activating Proteins / Q000235:genetics*; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology* / Q000235:genetics*
D058927:5-Lipoxygenase-Activating Proteins; C548592:ALOX5AP protein, human; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C517376:PDE4D protein, human
ALOX5AP; PDE4D; cerebral infarction; interaction; mutation; risk