Association of inflammatory response gene polymorphism with atherothrombotic stroke in Northern Han Chinese.
Atherosclerosis is an important pathophysiological basis of atherothrombotic stroke (ATS), and inflammation plays a significant role in atherosclerosis formation. In this study, single-nucleotide polymorphisms (SNPs) in three key inflammation-related genes, 5-lipoxygenase activating protein (ALOX5AP), phosphodiesterase 4D (PDE4D), and interleukin-1α (IL-1α), were investigated to determine their association with ATS in Northern Han Chinese. Six-hundred and eighty-two ATS patients and 598 unrelated controls were recruited. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism and matrix-assisted laser desorption ionization time-of-flight mass spectrometry primer extension. The genotype and allele frequencies of each SNP were statistically analyzed. Risk of ATS was found for the ALOX5AP SG13S114A/T AA genotype (P = 0.040) and A allele (P = 0.033), PDE4D SNP83C/T TT genotype (P = 0.010) and T allele (P = 0.008) and SNP219A/G GG genotype (P = 0.025) and G allele (P = 0.022), and the IL-1α-889C/T T allele (P = 0.035). The differences still remained significant after adjustment. The ALOX5AP HapA haplotype was not correlated with ATS (P = 0.834), but GCGA represented an at-risk haplotype (P = 0.008). Furthermore, the PDE4D AA haplotype at SNP219-220 might be an at-risk haplotype (P = 0.013), while GA might be a protective haplotype (P = 0.005). The ALOX5AP (SG13S114A/T), PDE4D (SNP83C/T, 219A/G), and IL-1α (-889C/T) SNPs were associated with an increased risk of ATS in Northern Han Chinese.
Department of Neurology,  the First Affiliated Hospital of China Medical University, Shenyang 110001,  China.
Jiuhan
J
Zhao
Xiaohong
X
Wang
Jialiang
J
Xu
Nan
N
Li
Xiuli
X
Shang
Zhiyi
Z
He
Jun
J
Yang
D058927:5-Lipoxygenase-Activating Proteins / Q000235:genetics*; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D050197:Atherosclerosis / Q000150:complications; D002545:Brain Ischemia / Q000150:complications; D002681:China; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3 / Q000235:genetics*; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007249:Inflammation / Q000150:complications; D053582:Interleukin-1alpha / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D020521:Stroke / Q000208:ethnology / Q000209:etiology / Q000235:genetics*; D013927:Thrombosis / Q000150:complications
D058927:5-Lipoxygenase-Activating Proteins; C548592:ALOX5AP protein, human; D053582:Interleukin-1alpha; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C517376:PDE4D protein, human