Jeon Yeonsu, Jeon Sungwon, An Kyungwhan, Kim Yeo Jin, Kim Byoung-Chul, Ryu Hyojung, Choi Whan-Hyuk, Choi HyunJoo, Kim Weon, Lee Sang Yeub, Bae Jang-Whan, Hwang Jin-Yong, Kang Min Gyu, An Seolbin, Kim Yeonkyung, Kang Younghui, Kim Byung Chul, Bhak Jong, Shin Eun-Seok
Korean Genomics Center (KOGIC), Ulsan National Institute of Science and Technology (UNIST), Ulsan, Republic of Korea.
Clinomics Inc., Ulsan, Republic of Korea.
Front Cardiovasc Med. 2023 Jul 3;10:1226971. doi: 10.3389/fcvm.2023.1226971. eCollection 2023.
Acute myocardial infarction (AMI) is one of the leading causes of death worldwide, and approximately half of AMI-related deaths occur before the affected individual reaches the hospital. The present study aimed to identify and validate genetic variants associated with AMI and their role as prognostic markers.
We conducted a replication study of 29 previously identified novel loci containing 85 genetic variants associated with early-onset AMI using a new independent set of 2,920 Koreans [88 patients with early- and 1,085 patients with late-onset AMI, who underwent percutaneous coronary intervention (PCI), and 1,747 healthy controls].
Of the 85 previously reported early-onset variants, six were confirmed in our genome-wide association study with a false discovery rate of less than 0.05. Notably, rs12639023, a cis-eQTL located in the intergenic region between and , significantly increased longitudinal cardiac mortality and recurrent AMI. is known to play a role in altering vascular permeability. Another variant, rs78631167, located upstream of and known to function in fibrinolysis, was moderately replicated in this study. By surveying the nearby genomic region around rs78631167, we identified a significant novel locus (rs8109584) located 13 bp downstream of rs78631167. The present study showed that six of the early-onset variants of AMI are applicable to both early- and late-onset cases.
Our results confirm markers that can potentially be utilized to predict, screen, prevent, and treat candidate patients with AMI and highlight the potential of rs12639023 as a prognostic marker for cardiac mortality in AMI.
急性心肌梗死（AMI）是全球主要的死亡原因之一，约一半与AMI相关的死亡发生在患者到达医院之前。本研究旨在识别和验证与AMI相关的基因变异及其作为预后标志物的作用。
我们使用一组新的2920名韩国独立样本[88例早发型AMI患者、1085例晚发型AMI患者，均接受了经皮冠状动脉介入治疗（PCI），以及1747名健康对照]，对先前鉴定的29个包含85个与早发型AMI相关基因变异的新位点进行了重复研究。
在先前报道的85个早发型变异中，有6个在我们的全基因组关联研究中得到确认，错误发现率小于0.05。值得注意的是，位于 和 之间基因间区域的顺式eQTL rs12639023显著增加了纵向心脏死亡率和复发性AMI。已知 在改变血管通透性方面起作用。另一个变异rs78631167位于 的上游，已知在纤维蛋白溶解中起作用，在本研究中得到了适度的重复验证。通过对rs78631167附近的基因组区域进行检测，我们在rs78631167下游13 bp处鉴定出一个重要的新位点（rs8109584）。本研究表明，AMI的6个早发型变异适用于早发型和晚发型病例。
我们的结果证实了可潜在用于预测、筛查、预防和治疗AMI候选患者的标志物，并突出了rs12639023作为AMI心脏死亡率预后标志物的潜力。
