Division of Cardiology, Johns Hopkins University School of Medicine, 4940 Eastern Avenue, Baltimore, MD 21224, United States of America.
Division of Cardiology, Johns Hopkins University School of Medicine, 4940 Eastern Avenue, Baltimore, MD 21224, United States of America.
Thromb Res. 2021 Apr;200:115-120. doi: 10.1016/j.thromres.2021.01.027. Epub 2021 Feb 6.
Genetic differences between races have been hypothesized to contribute to differences in outcome from acute coronary syndromes (ACS). Our objective was to assess racial differences in genetic variations in the platelet serotonin transporter (5HTT) and receptor in patients with ACS.
127 consecutive patients, African Americans (AA) = 27; Caucasian (C) =100, admitted with ACS were evaluated for platelet function by serotonin (5HT) induced platelet activation. All patients were genotyped for two polymorphisms in the serotonin-transporter-linked polymorphic region (5-HTTLPR) S/L and L/L and one polymorphism of the serotonin 2A receptor (5-HT2A, T102C) gene. All patients were followed for major and minor adverse cardiac events at 12 months.
AA when compared to C had a lower prevalence of the HTTLPR S allele (21% vs 45%, p = 0.0003) and a higher prevalence of the L allele (24% vs 4.5%, p = 0.0001). Allelic frequency of the 5-HT2A T102C allele was not significantly different between the races. Platelet activation was lower in AA compared to C, median EC50 5HT was 12.08 μg vs 2.14 μg (p = 0.001). The 5-HTTLPR and the 5-HT2A polymorphisms were not associated with platelet functional responses to serotonin. There were no significant differences in major or minor adverse cardiac events in patients with serotonin transporter or receptor polymorphisms.
We found a lower prevalence of the S allele and a higher prevalence of the G allele in AA with ACS. We also found decreased platelet activation in AA which did not correlate with serotonin-related platelet polymorphisms. It is unclear if other contributing factors may explain these platelet functional differences.
种族间的遗传差异被假设为导致急性冠状动脉综合征(ACS)结局差异的原因之一。我们的目的是评估 ACS 患者血小板 5-羟色胺转运体(5HTT)和受体的遗传变异在种族间的差异。
连续评估了 127 例 ACS 患者,其中非裔美国人(AA)=27 例;白种人(C)=100 例,评估血小板功能通过 5-羟色胺(5HT)诱导血小板活化。所有患者均进行了 5-羟色胺转运体连接多态区(5-HTTLPR)S/L 和 L/L 两个多态性和 5-羟色胺 2A 受体(5-HT2A,T102C)基因的一个多态性的基因分型。所有患者在 12 个月时随访主要和次要不良心脏事件。
与 C 相比,AA 具有较低的 HTTLPR S 等位基因的发生率(21%比 45%,p=0.0003)和较高的 L 等位基因的发生率(24%比 4.5%,p=0.0001)。种族间 5-HT2A T102C 等位基因的等位基因频率无显著差异。与 C 相比,AA 的血小板活化率较低,中位 EC50 5HT 为 12.08μg比 2.14μg(p=0.001)。5-HTTLPR 和 5-HT2A 多态性与血小板对 5-羟色胺的功能反应无关。在具有 5-羟色胺转运体或受体多态性的患者中,主要或次要不良心脏事件无显著差异。
我们发现 ACS 的 AA 中 S 等位基因的发生率较低,G 等位基因的发生率较高。我们还发现 AA 中的血小板活化减少,但与 5-羟色胺相关的血小板多态性无关。尚不清楚是否有其他因素可以解释这些血小板功能差异。