Department of Emergency, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Chin Med J (Engl). 2013 Jan;126(2):254-9.
Leukotrienes are arachidonic acid derivatives long known for their inflammatory properties. Leukotriene-based inflammation has been demonstrated to play a crucial role in atherosclerosis, a major risk factor for several human diseases. Recently, human genetic studies from us and others suggest that single nucleotide polymorphisms (SNPs) in leukotriene pathway genes influence the risk of atherosclerotic diseases such as stroke. This study aimed to assess the role of additional leukotriene pathway genes as a stroke risk factor within the Chinese Han population.
We sequenced the promoter, exonic, and intronic regions of leukotriene A4 hydrolase (LTA4H) and arachidonate 5-lipoxygenase (ALOX5), and then genotyped five SNPs in LTA4H and four SNPs in ALOX5 among 691 cases with stroke and 732 controls from the Chinese population.
We detected a significant association between an intronic SNP in LTA4H (rs6538697) and stroke in our subjects (adjusted odds ratio, recessive model, 1.75; P = 0.022); and the SNP rs2029253 in ALOX5 was associated with a decreased risk of stroke (adjusted odds ratio, 0.76; 95% confidence interval, 0.59 - 0.97).
Genetic variants in LTA4H and ALOX5 may modulate the risk of stroke in the Chinese Han population.
白三烯是花生四烯酸的衍生物,长期以来因其炎症特性而为人所知。白三烯炎症已被证明在动脉粥样硬化中起着关键作用,动脉粥样硬化是多种人类疾病的主要危险因素。最近,我们和其他人的人类遗传研究表明,白三烯途径基因中的单核苷酸多态性(SNP)影响动脉粥样硬化疾病(如中风)的风险。本研究旨在评估白三烯途径基因的其他基因作为汉族人群中风风险因素的作用。
我们对 LTA4H 和 ALOX5 的启动子、外显子和内含子区域进行了测序,然后对汉族人群的 691 例中风病例和 732 例对照者中的 LTA4H 中的 5 个 SNP 和 ALOX5 中的 4 个 SNP 进行了基因分型。
我们在研究对象中检测到 LTA4H 内含子 SNP(rs6538697)与中风之间存在显著关联(调整后的优势比,隐性模型,1.75;P=0.022);ALOX5 中的 SNP(rs2029253)与中风风险降低相关(调整后的优势比,0.76;95%置信区间,0.59-0.97)。
LTA4H 和 ALOX5 中的遗传变异可能调节汉族人群中风的风险。