Key result
ALOX5AP, PDE4D, and IL-1α gene polymorphisms are linked to increased atherothrombotic stroke risk.
Why the study?
Inflammation plays a significant role in atherosclerosis formation, but the association of inflammatory gene polymorphisms with atherothrombotic stroke in Northern Han Chinese was unclear.
Are single-nucleotide polymorphisms in ALOX5AP, PDE4D, and IL-1α genes associated with an increased risk of atherothrombotic stroke in Northern Han Chinese?
Case-Control (n=1,280)
Are single-nucleotide polymorphisms in ALOX5AP, PDE4D, and IL-1α genes associated with an increased risk of atherothrombotic stroke in Northern Han Chinese?
p-value: p=0.040
Specific single-nucleotide polymorphisms in the ALOX5AP, PDE4D, and IL-1α genes are associated with an increased risk of atherothrombotic stroke in the Northern Han Chinese population.
SNP associations with ATS in Northern Han Chinese are hypothesis-generating; leaves open any role in risk prediction or targeted therapy.
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.
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Zhao et al. (2012) conducted a case-control in Atherothrombotic stroke (n=1,280). Inflammatory response gene polymorphisms (ALOX5AP, PDE4D, IL-1α) vs. Unrelated controls was evaluated on Risk of atherothrombotic stroke (p=0.040). Polymorphisms in the ALOX5AP, PDE4D, and IL-1α genes were significantly associated with an increased risk of atherothrombotic stroke in Northern Han Chinese.
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