Increased platelet aggregability associated with platelet GPIIIα PlA2 polymorphism -: The Framingham Offspring Study
Increased platelet aggregability associated with platelet GPIIIα PlA2 polymorphism -: The Framingham Offspring Study
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DOI：
10.1161/01.atv.19.4.1142
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发表时间：
1999-04-01
影响因子：
8.7
通讯作者：
Tofler, GH
中科院分区：
文献类型：
--
作者：
Feng, DL;Lindpaintner, K;Tofler, GH
血小板糖蛋白IIb/IIIa（GP IIb/IIIa）在血小板聚集中起关键作用。最近的数据表明，GPIIIa的P1（A2）多态性可能与心血管疾病的风险增加有关。然而，目前尚不清楚这种多态性与血小板反应性之间是否存在任何关联。我们确定了1422例来自Frachial Offspring研究的受试者的GP IIIa基因型和血小板反应性表型数据。采用基于PCR的限制性片段长度多态性分析进行基因分型。血小板聚集性用Born法测定。测定肾上腺素和ADP的阈浓度。P1（A1）和P1（A2）等位基因频率分别为0.84和0.16。1或2个P1（A2）等位基因的存在与血小板聚集性增加有关，如肾上腺素和ADP的阈值浓度逐渐降低所示。对于肾上腺素，纯合子Pl（A1）的平均浓度为0.9 μ mol/L（0.9至1.0），杂合子Pl（A1）/Pl（A2）为0.7 mmol/L（0.7至0.9），纯合子Pl（A2）个体为0.6 μ mol/L（0.4至1.0），P=0.009。调整协变量后，肾上腺素诱导的聚集性增加仍具有高度显著性（P=0.007）。对于ADP诱导的聚集，相应的平均浓度为3.1 μ mol/L（3.0 - 3.2）、3.0 μ mol/L（2.9 - 3.2）和2.8 μ mol/L（2.4 - 3.3）;校正协变量后P=0.19。我们的研究结果表明，编码GP IIIa的基因的分子变体在体外血小板反应性中发挥作用。我们的观察结果与所报道的P1（A2）同种异型与心血管疾病风险增加的相关性是一致的，并提供了解释。
The platelet glycoprotein IIb/IIIa (GP IIb/IIIa) plays a pivotal role in platelet aggregation. Recent data suggest that the Pl(A2) polymorphism of GPIIIa may be associated with an increased risk for cardiovascular disease. However, it is unknown if there is any association between this polymorphism and platelet reactivity. We determined GP IIIa genotype and platelet reactivity phenotype data in 1422 subjects from the Framingham Offspring Study. Genotyping was performed using PCR-based restriction fragment length polymorphism analysis. Platelet aggregability was evaluated by the Born method. The threshold concentrations of epinephrine and ADP were determined. Allele frequencies of Pl(A1) and Pl(A2) were 0.84 and 0.16, respectively. The presence of 1 or 2 Pl(A2) alleles was associated with increased platelet aggregability as indicated by incrementally lower threshold concentrations for epinephrine and ADP. For epinephrine, the mean concentrations were 0.9 mu mol/L (0.9 to 1.0) for homozygous Pl(A1), 0.7 mmol/L (0.7 to 0.9) for the heterozygous Pl(A1)/Pl(A2), and 0.6 mu mol/L (0.4 to 1.0) for homozygous Pl(A2) individuals, P=0.009. The increase in aggregability induced by epinephrine remained highly significant (P=0.007) after adjustment for covariates. For ADP-induced aggregation, the respective mean concentrations were 3.1 mu mol/L (3.0 to 3.2), 3.0 mu mol/L (2.9 to 3.2), and 2.8 mu mol/L (2.4 to 3.3); P=0.19 after adjustment for covariates. Our findings indicate that molecular variants of the gene encoding GP IIIa play a role in platelet reactivity in vitro. Our observations are compatible with and provide an explanation for the reported association of the Pl(A2) allotype with increased risk for cardiovascular disease.