Functional consequences of the prothrombotic SERPINC1 rs2227589 polymorphism on antithrombin levels
Functional consequences of the prothrombotic SERPINC1 rs2227589 polymorphism on antithrombin levels
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DOI：
10.3324/haematol.2008.000604
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发表时间：
2009-04-01
期刊：
影响因子：
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通讯作者：
Sanchez-Vega, Beatriz
中科院分区：
文献类型：
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作者：
Anton, Ana I.;Teruel, Raul;Sanchez-Vega, Beatriz
参与抗凝血酶个体间变异的遗传因素尚未确定。我们研究了298名西班牙高加索献血者抗凝血酶基因编码基因(SERPINC1)的两个多态：位于启动子区域的DNA长度多态rs3138521和位于内含子1的SNP rs2227589，该基因被认为是轻微的血栓形成危险因素。我们检测到这些多态之间存在完全连锁不平衡(D‘=0.999)。Rs3138521基因多态没有功能性后果。然而，rs2227589SNP与血浆抗FXA活性和抗凝血酶水平显著相关：A等位基因携带者的抗凝活性和水平略低于GG患者(97.0+/-7.3%vs.94.6+/-8.4%；p=0.032；99.5+/-5.8%vs.94.8+/-5.6%；p=0.001)。我们的结果发现，rs2227589多态的功能效应不能通过它与启动子多态的关联来解释，该多态支持与A等位基因相关的中等血栓风险。
Genetic factors involved in the interindividual variability of antithrombin have not been identified. We studied two polymorphisms of the gene coding for antithrombin (SERPINC1) in 298 Spanish Caucasian blood donors: rs3138521, a DNA length polymorphism located on the promoter region and rs2227589, a SNP located on intron 1 that has been described as a mild thrombotic risk factor. We detected a complete linkage disequilibrium between these polymorphisms (D'=0.999). The rs3138521 polymorphism has no functional consequences. However, the rs2227589 SNP significantly associated with plasma anti-FXa activity and antithrombin levels: carriers of the A allele had slightly but significantly lower anticoagulant activity and levels than GG subjects (97.0 +/- 7.3% vs. 94.6 +/- 8.4%; p=0.032; 99.5 +/- 5.8% vs. 94.8 +/- 5.6%; p=0.001; respectively). Our results identified a functional effect of the rs2227589 polymorphism not explained by its linkage with the promoter polymorphism that support the moderate thrombotic risk associated with the A allele.