医学
冠状动脉疾病
内科学
ABO血型系统
等位基因
阿司匹林
花生四烯酸
血小板
血小板活化
心肌梗塞
基因座(遗传学)
胃肠病学
心脏病学
遗传学
生物
生物化学
基因
酶
作者
Morten Krogh Christiansen,Susan Weng Larsen,Mette Nyegaard,Søs Neergaard‐Petersen,Morten Würtz,Erik Lerkevang Grove,Anne‐Mette Hvas,Henrik Kjærulf Jensen,Steen Dalby Kristensen
标识
DOI:10.1016/j.ijcard.2019.01.090
摘要
Genome-wide association studies of patients with coronary artery disease (CAD) suggest that several risk loci increase the risk of CAD and myocardial infarction (MI) equally. In contrast, the ABO locus is stronger associated with MI than with CAD, but the underlying mechanisms are unknown.To investigate the association between the ABO risk variant and platelet activation and aggregation. Moreover, to explore the effects of other CAD-associated risk variants.We included 879 stable CAD patients receiving low-dose aspirin. All patients were genotyped for 45 genome-wide significant CAD risk variants, including rs495828 at the ABO locus. A genetic risk score (GRS) was calculated to assess the combined risk of all genetic variants. Serum soluble P-selectin (sP-selectin) and thromboxane B2 were used as measures of platelet activation, and platelet aggregation was assessed by multiple electrode aggregometry (MEA) using arachidonic acid and collagen as agonists and VerifyNow.The rs495828 CAD risk allele was associated with higher MEA platelet aggregation; arachidonic acid: 14.9% (6.7-23.7%, p = 0.0002) higher AUC (Area Under aggregation Curve) per risk allele, and collagen: 13.1% (5.8%-20.9%, p = 0.0003). Conversely, sP-selectin levels were 7.5% (3.1%-11.7%, p = 0.001) lower per risk allele. Rs495828 genotypes were not associated with aggregation assessed by VerifyNow (p = 0.30) or S-thromboxane B2 levels (p = 0.98). None of the remaining variants or the GRS were associated with platelet activation or aggregation.The ABO risk allele was associated with increased platelet aggregation as assessed by MEA. This finding may contribute to explain the increased MI risk in ABO risk variant carriers.
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