Polymorphism in the fractalkine receptor CX3CR1 as a genetic risk factor for coronary artery disease
Polymorphism in the fractalkine receptor CX3CR1 as a genetic risk factor for coronary artery disease
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DOI：
10.1182/blood.v97.7.1925
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发表时间：
2001-04-01
期刊：
影响因子：
20.3
通讯作者：
Combadière, C
中科院分区：
文献类型：
--
作者：
Moatti, D;Faure, S;Combadière, C
冠状动脉粥样硬化是工业化国家死亡的主要原因，在动脉粥样硬化中起关键作用的单核细胞可能在特定的趋化剂和粘附分子的引导下迁移到血管壁中。这一作用的一个引人注目的候选者是趋化因子受体 CX3CR1，它在单核细胞上表达，并充当趋化受体或粘附分子，具体取决于其配体 fractalkine 是游离存在还是膜结合。最近发现了 CX3CR1 的一个常见变体，由等位基因 I249 和 M280 编码，形成常见的 I249M280 单倍型。当对 151 名急性冠状动脉综合征患者和 249 名健康对照者进行 CX3CR1 基因型分析时，CX3CR1 I249 杂合性与急性冠状动脉事件风险显着降低相关，与已确定的获得性冠状动脉危险因素无关。糖尿病）。该等位基因的调整后优势比为 0.43（95% 置信区间，0.26-0.72；P =.001）。与此一致的是，外周血单核细胞的功能分析表明，CX3CR1 I249 杂合性与每个细胞的 fractalkine 结合位点数量显着减少相关。结果表明，CX3CR1 I249是冠状动脉疾病的独立遗传危险因素，CX3CR1可能参与动脉粥样硬化性疾病的发病机制。 (Blood, 2001;97: 1925-1928) (C) 2001 年，美国血液学会。
Coronary atherosclerosis is a major cause of death in industrialized countries, Monocytes, which play a key role in atherosclerosis, migrate into the vessel wall, presumably guided by specific chemoattractant and adhesion molecules. A compelling candidate for this role is the chemokine receptor CX3CR1,which is expressed on monocytes and acts as either a chemotactic receptor or an adhesion molecule, depending on whether its ligand, fractalkine, is presented free or membrane bound. A common variant of CX3CR1 was recently identified, encoded by the alleles I249 and M280, which form a common I249M280 haplotype, When CX3CR1 genotypes were analyzed in 151 patients with acute coronary syndromes and in 249 healthy controls, CX3CR1 I249 heterozygosity was associated with a markedly reduced risk of acute coronary events, independent of established acquired coronary risk factors leg, smoking, diabetes). The adjusted odds ratio for this allele was 0.43 (95% confidence interval, 0.26-0.72; P =.001). Consistent with this, functional analysis of peripheral blood mononuclear cells showed that CX3CR1 I249 heterozygosity was associated with a significant decrease in the number of fractalkine binding sites per cell. The results show that CX3CR1 I249 is an independent genetic risk factor for coronary artery disease and that CX3CR1 may be involved in the pathogenesis of atherosclerotic disease. (Blood, 2001;97: 1925-1928) (C) 2001 by The American Society of Hematology.