Division of Angiology, Department of Internal Medicine II, Medical University, Vienna, Austria.
Eur J Clin Invest. 2011 Apr;41(4):365-71. doi: 10.1111/j.1365-2362.2010.02416.x. Epub 2010 Nov 4.
A single-nucleotide polymorphism (SNP) in the palladin gene (PALLD, rs7439293) has recently been reported to be associated with coronary heart disease (CHD) in two case-control studies as well as in a large population-based cohort (Atherosclerosis Risk in Communities study, ARIC). Its clinical relevance, however, has not been evaluated prospectively. We investigated whether the risk allele (A) of PALLD rs7439293 (G>A) is associated with the occurrence of future major cardiovascular events (MACE) in a cohort of patients with prevalent carotid atherosclerosis.
A total of 1283 consecutive patients with neurologically asymptomatic carotid atherosclerosis were included in the study and prospectively followed for a median of 3·5 years (interquartile range 3-4 years). We analysed whether the risk allele is associated with progression of carotid atherosclerosis after a 6-9-month period as measured by duplex Doppler sonography. Patients were then followed for the occurrence of a first MACE, a composite of myocardial infarction, stroke, coronary revascularization and death.
After a median of 7·5 months (interquartile range 6-9 months), progression of carotid stenosis was observed in 103 (8·1%) patients. Cardiovascular events occurred in 337 (30%) patients after a median follow-up of 3·5 years. The risk allele of PALLD was neither associated with progressive carotid atherosclerosis (P = 0·21) nor with MACE (P = 0·58). Adjusted hazard ratios for a first MACE in heterozygous and homozygous carriers were 0·83 (95% CI 0·58-1·18) and 0·94 (95% CI 0·65-1·35) compared to wild type, respectively.
The A-allele of PALLD rs7439293 was not associated with progressive carotid atherosclerosis as measured by duplex Doppler sonography nor did it represent a risk factor for adverse cardiovascular outcome among patients with prevalent carotid atherosclerosis.
最近的两项病例对照研究以及一项大型基于人群的队列研究(社区动脉粥样硬化风险研究,ARIC)报道,帕拉丁基因(PALLD,rs7439293)中的单核苷酸多态性(SNP)与冠心病(CHD)有关。然而,其临床相关性尚未进行前瞻性评估。我们调查了 PALLD rs7439293(G>A)的风险等位基因(A)是否与患有颈动脉粥样硬化的患者未来主要心血管事件(MACE)的发生有关。
共纳入 1283 例连续的、有神经症状的颈动脉粥样硬化患者,进行前瞻性随访,中位随访时间为 3.5 年(四分位间距为 3-4 年)。我们分析了在 6-9 个月的时间内,通过双功能超声多普勒测量颈动脉狭窄进展时,风险等位基因是否与颈动脉粥样硬化的进展有关。然后,对患者进行首次 MACE(心肌梗死、中风、冠状动脉血运重建和死亡的复合终点)的发生情况进行随访。
中位随访 7.5 个月(四分位间距 6-9 个月)后,103 例(8.1%)患者发生颈动脉狭窄进展。中位随访 3.5 年后,337 例(30%)患者发生心血管事件。PALLD 的风险等位基因与颈动脉粥样硬化的进展(P=0.21)或 MACE(P=0.58)均无关。杂合子和纯合子携带者首次发生 MACE 的调整后的风险比分别为 0.83(95%CI 0.58-1.18)和 0.94(95%CI 0.65-1.35)。
PALLD rs7439293 的 A 等位基因与双功能超声多普勒测量的颈动脉粥样硬化进展无关,也不能作为患有颈动脉粥样硬化的患者不良心血管结局的危险因素。