Fan Yujia, Chen Hui, Li Aifan, Shi Yunshu, Zhang Yuchao, Feng Qingchuan, Sun Yan, Zheng Hong, He Ying
Department of Cell Biology and Medical Genetics, Basic Medical College of Zhengzhou University, Zhengzhou, China.
Department of Neurology, the First People Hospital of Zhengzhou, Zhengzhou, China.
PLoS One. 2015 Mar 27;10(3):e0122393. doi: 10.1371/journal.pone.0122393. eCollection 2015.
No coding sequence variants of the gene encoding 5-lipoxygenase-activating protein (ALOX5AP) leading to amino acid substitutions have been identified. Therefore, variants in the ALOX5AP promoter region have received attention recently. The purpose of this study was to explore whether the promoter polymorphism rs17222919 is involved in the etiology of ischemic stroke (IS) in the Chinese Han population. We investigated the rs17222919 polymorphism by TaqMan genotyping in two independent Chinese Han samples: the first comprised 910 IS patients and 925 healthy inhabitants from the northern Henan Province, while the second included 1003 IS patients and 889 healthy controls from the southern Henan Province. Functional characterization of rs17222919 was performed by an in vitro luciferase assay. After adjusting for conventional risk factors, the G allele frequencies in the IS groups were significantly lower than that in the control groups of the two independent Chinese cohorts (19.0% vs. 22.9%, P = 0.004, odds ratio (OR) = 0.792, 95% confidence interval (CI) = 0.675-0.929; 18.8% vs. 22.9%, P = 0.002, OR = 0.782, 95% CI = 0.668-0.915, respectively). This was also observed in the large-artery atherosclerosis (LAA) and stroke of other undetermined etiology (SUE) subtypes (P = 0.019, OR = 0.815, 95% CI = 0.687-0.967; P = 0.021, OR = 0.815, 95% CI = 0.685-0.970, respectively). Additionally, the TG genotype and G allele frequencies were significantly lower in the IS compared with the control group in two female cohorts (P<0.05). Finally, the in vitro luciferase assay demonstrated that the G allele has a significantly lower transcription activity than the T allele (P = 0.031). Our study provides evidence that the promoter single nucleotide polymorphism (SNP) rs17222919 is a potential genetic protective factor for IS in the Chinese Han population.
尚未发现编码5-脂氧合酶激活蛋白（ALOX5AP）的基因存在导致氨基酸替换的编码序列变异。因此，ALOX5AP启动子区域的变异最近受到了关注。本研究的目的是探讨启动子多态性rs17222919是否参与中国汉族人群缺血性卒中（IS）的病因。我们通过TaqMan基因分型在两个独立的中国汉族样本中研究了rs17222919多态性：第一个样本包括来自河南省北部的910例IS患者和925名健康居民，而第二个样本包括来自河南省南部的1003例IS患者和889名健康对照。通过体外荧光素酶测定对rs17222919进行功能表征。在调整传统危险因素后，两个独立中国队列的IS组中G等位基因频率显著低于对照组（分别为19.0%对22.9%，P = 0.004，比值比（OR）= 0.792，95%置信区间（CI）= 0.675 - 0.929；18.8%对22.9%，P = 0.002，OR = 0.782，95% CI = 0.668 - 0.915）。在大动脉粥样硬化（LAA）和其他病因未明的卒中（SUE）亚型中也观察到了这一现象（分别为P = 0.019，OR = 0.815，95% CI = 0.687 - 0.967；P = 0.021，OR = 0.815，95% CI = 0.685 - 0.970）。此外，在两个女性队列中，IS组的TG基因型和G等位基因频率显著低于对照组（P<0.05）。最后，体外荧光素酶测定表明，G等位基因的转录活性显著低于T等位基因（P = 0.031）。我们的研究提供了证据，表明启动子单核苷酸多态性（SNP）rs17222919是中国汉族人群IS的潜在遗传保护因素。
