Genetic Variation in the Leukotriene Pathway and Carotid Intima-Media Thickness A 2-Stage Replication Study
Genetic Variation in the Leukotriene Pathway and Carotid Intima-Media Thickness A 2-Stage Replication Study
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DOI：
10.1161/strokeaha.108.525733
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发表时间：
2009-03-01
期刊：
影响因子：
8.3
通讯作者：
Markus, Hugh S.
中科院分区：
文献类型：
--
作者：
Bevan, Steve;Lorenz, Matthias W.;Markus, Hugh S.
背景与目的——近期发现白三烯生物合成途径中的基因变异可能会增加缺血性卒中和动脉粥样硬化的风险，这表明白三烯家族可能是心血管疾病的潜在介质。我们采用两阶段重复设计，检测了该途径相关的8个基因的多态性是否与颈动脉内膜 - 中层厚度所衡量的早期动脉粥样硬化和重塑有关。
方法——我们对来自颈动脉粥样硬化进展研究（CAPS）的969名个体（一项基于社区的正常受试者研究）进行了评估，检测了白三烯途径中的39种变异。在初始队列中发现21种变异存在显著关联以及基因 - 环境相互作用，并在来自同一CAPS人群的接下来的1905例连续病例中进行了检测。
结果——在进行多重检验校正后，任何单个多态性与颈动脉内膜 - 中层厚度本身之间均未发现可重复的关联。在分叉处内膜 - 中层厚度的rs17222814与每日饮酒超过30克之间重复出现了一种单一的基因 - 环境相互作用。
结论——我们所检测的白三烯生物合成途径中的基因变异对由颈动脉内膜 - 中层厚度所确定的早期动脉粥样硬化和重塑风险影响很小。我们的研究不能排除它们是动脉粥样硬化进程更晚期阶段的风险因素。（《卒中》2009年；40卷：696 - 701页）
Background and Purpose-The recent finding that genetic variation in the leukotriene biosynthesis pathway may confer an increased risk of ischemic stroke and atherosclerosis has implicated the leukotriene family as potential mediators of cardiovascular disease. Using a 2-stage replication design, we have examined whether polymorphisms in 8 genes related to this pathway are associated with early atherosclerosis and remodeling as measured by carotid artery intima-media thickness.Methods-We assessed 969 individuals from the Carotid Atherosclerosis Progression Study ( CAPS), a community based study of normal subjects, for 39 variants in the leukotriene pathway. Significant associations and gene-environment interactions were found for 21 variants in the initial cohort and were examined in the next 1905 consecutive cases from the same CAPS population.Results-No replicable association between any individual polymorphism and carotid intima-media thickness itself was present after correction for multiple testing. A single gene-environment interaction was replicated between rs17222814 on bifurcation intima-media thickness and alcohol consumption exceeding 30 grams per day.Conclusion-The genetic variants we examined in the leukotriene biosynthesis pathway have little effect on early atherosclerosis and remodeling risk as determined by carotid intima-media thickness. Our study cannot exclude them as being risk factors for more advanced stages in the atherosclerotic process. (Stroke. 2009; 40: 696-701.)