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. 2023 Jul 3:10:1226971.
doi: 10.3389/fcvm.2023.1226971. eCollection 2023.

Identification and validation of six acute myocardial infarction-associated variants, including a novel prognostic marker for cardiac mortality

Yeonsu Jeon #  1   2 , Sungwon Jeon #  2 , Kyungwhan An  1   3 , Yeo Jin Kim  2 , Byoung-Chul Kim  2 , Hyojung Ryu  2 , Whan-Hyuk Choi  4 , HyunJoo Choi  1   3 , Weon Kim  5 , Sang Yeub Lee  6 , Jang-Whan Bae  7 , Jin-Yong Hwang  8 , Min Gyu Kang  8 , Seolbin An  1   3 , Yeonkyung Kim  2 , Younghui Kang  2 , Byung Chul Kim  2 , Jong Bhak  1   2   3   9 , Eun-Seok Shin  10
Affiliations

Identification and validation of six acute myocardial infarction-associated variants, including a novel prognostic marker for cardiac mortality

Yeonsu Jeon et al. Front Cardiovasc Med. .

Abstract

Background: 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.

Materials and methods: 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].

Results: 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 LINC02005 and CNTN3, significantly increased longitudinal cardiac mortality and recurrent AMI. CNTN3 is known to play a role in altering vascular permeability. Another variant, rs78631167, located upstream of PLAUR 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.

Conclusion: 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.

Keywords: acute myocardial infarction; cardiac mortality; genetic marker; genome-wide association study; prognostic marker.

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Conflict of interest statement

YJ, SJ, B-CK, HR, YeK, YoK, BK, and YK were employed by Clinomics Inc. JB is a CEO of Clinomics Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Validation process workflow for genetic variants associated with acute myocardial infarction (AMI).
Figure 2
Figure 2
Genetic effects on cardiac mortality and recurrent acute myocardial infarction (AMI). (A,B) Comparison of allele frequencies among cardiac death, alive and control groups in (A) rs12639023, LINC02005-CNTN3 and (B) rs12639020, LINC02005-CNTN3. (C,D) Kaplan–Meier curves for two variants with a positive genetic effect for cardiac mortality and recurrent AMI. (C) Survival curve by rs12639023 genotype. (D) Survival curve by rs12639020 genotype. X-axis denotes days from enrollment to death or last follow-up. Y-axis denotes event-free survival probability. Event means cardiac mortality and recurrent AMI.
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