家族性高胆固醇血症中的膜联蛋白A5单倍型：与颈动脉内膜中层厚度及心血管疾病风险无关。
Annexin A5 haplotypes in familial hypercholesterolemia: lack of association with carotid intima-media thickness and cardiovascular disease risk.
作者信息
Hiddink Larissa, Dallinga-Thie Geesje M, Hovingh G Kees, de Visser Marieke C H, Peer Petronella G M, Stalenhoef Anton F H, van Heerde Waander L
机构信息
Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Geert Grooteplein 10, 6525 GA Nijmegen, The Netherlands.
Department of Vascular Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
出版信息
Atherosclerosis. 2015 Feb;238(2):195-200. doi: 10.1016/j.atherosclerosis.2014.11.023. Epub 2014 Nov 29.
OBJECTIVE
Annexin A5 (ANXA5) has been suggested to possess antiatherogenic properties. We investigated whether ANXA5 genetic variations and plasma ANXA5 levels were associated with carotid atherosclerosis and contributed to cardiovascular disease (CVD) risk in patients with familial hypercholesterolemia (FH).
METHODS
We sequenced the promoter region and exon 2 of ANXA5 in 284 FH patients from the ASAP (Atorvastatin versus Simvastatin on Atherosclerosis Progression) trial. Common haplotypes (H) were constructed based on seven single nucleotide polymorphisms (SNPs). We studied whether plasma ANXA5 levels or ANXA5 haplotypes were associated with the extent of atherosclerosis (evaluated by carotid intima-media thickness (IMT). The association between ANXA5 haplotypes and the risk for CVD events was investigated in 1730 FH patients from the GIRaFH (Genetic Identification of Risk factors in Familial Hypercholesterolemia) study.
RESULTS
In ASAP, individuals carrying the ANXA5 haplotype H2 exhibited lower plasma ANXA5 levels, whereas H4 carriers had increased levels of circulating ANXA5 compared to non-carriers. Plasma ANXA5 levels were not associated with carotid IMT. None of the four ANXA5 haplotypes correlated with the age-related IMT progression (ASAP study) or contributed to CVD risk (GIRaFH cohort).
CONCLUSIONS
Both ANXA5 haplotypes and plasma ANXA5 levels were not associated with carotid IMT progression or CVD risk in FH patients.
目的
有人提出膜联蛋白A5（ANXA5）具有抗动脉粥样硬化特性。我们研究了ANXA5基因变异和血浆ANXA5水平是否与家族性高胆固醇血症（FH）患者的颈动脉粥样硬化相关，并对心血管疾病（CVD）风险有影响。
方法
我们对来自ASAP（阿托伐他汀与辛伐他汀对动脉粥样硬化进展的影响）试验的284例FH患者的ANXA5启动子区域和外显子2进行了测序。基于7个单核苷酸多态性（SNP）构建了常见单倍型（H）。我们研究了血浆ANXA5水平或ANXA5单倍型是否与动脉粥样硬化程度相关（通过颈动脉内膜中层厚度（IMT）评估）。在来自GIRaFH（家族性高胆固醇血症风险因素的基因鉴定）研究的1730例FH患者中，研究了ANXA5单倍型与CVD事件风险之间的关联。
结果
在ASAP研究中，携带ANXA5单倍型H2的个体血浆ANXA5水平较低，而与非携带者相比，H4携带者的循环ANXA5水平升高。血浆ANXA5水平与颈动脉IMT无关。四种ANXA5单倍型均与年龄相关的IMT进展（ASAP研究）无关，也未对CVD风险产生影响（GIRaFH队列）。
结论
在FH患者中，ANXA5单倍型和血浆ANXA5水平均与颈动脉IMT进展或CVD风险无关。
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