Identification and validation of six acute myocardial infarction-associated variants, including a novel prognostic marker for cardiac mortality
BackgroundAcute 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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-07-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2023.1226971/full |
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| author | Yeonsu Jeon Yeonsu Jeon Sungwon Jeon Kyungwhan An Kyungwhan An Yeo Jin Kim Byoung-Chul Kim Hyojung Ryu Whan-Hyuk Choi HyunJoo Choi HyunJoo Choi Weon Kim Sang Yeub Lee Jang-Whan Bae Jin-Yong Hwang Min Gyu Kang Seolbin An Seolbin An Yeonkyung Kim Younghui Kang Byung Chul Kim Jong Bhak Jong Bhak Jong Bhak Jong Bhak Eun-Seok Shin |
| author_facet | Yeonsu Jeon Yeonsu Jeon Sungwon Jeon Kyungwhan An Kyungwhan An Yeo Jin Kim Byoung-Chul Kim Hyojung Ryu Whan-Hyuk Choi HyunJoo Choi HyunJoo Choi Weon Kim Sang Yeub Lee Jang-Whan Bae Jin-Yong Hwang Min Gyu Kang Seolbin An Seolbin An Yeonkyung Kim Younghui Kang Byung Chul Kim Jong Bhak Jong Bhak Jong Bhak Jong Bhak Eun-Seok Shin |
| author_sort | Yeonsu Jeon |
| collection | DOAJ |
| description | BackgroundAcute 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 methodsWe 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].ResultsOf 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.ConclusionOur 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. |
| first_indexed | 2024-03-13T01:47:18Z |
| format | Article |
| id | doaj.art-261fece31fc3432bbeea71d89d801e73 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-03-13T01:47:18Z |
| publishDate | 2023-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-261fece31fc3432bbeea71d89d801e732023-07-03T05:38:19ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2023-07-011010.3389/fcvm.2023.12269711226971Identification and validation of six acute myocardial infarction-associated variants, including a novel prognostic marker for cardiac mortalityYeonsu Jeon0Yeonsu Jeon1Sungwon Jeon2Kyungwhan An3Kyungwhan An4Yeo Jin Kim5Byoung-Chul Kim6Hyojung Ryu7Whan-Hyuk Choi8HyunJoo Choi9HyunJoo Choi10Weon Kim11Sang Yeub Lee12Jang-Whan Bae13Jin-Yong Hwang14Min Gyu Kang15Seolbin An16Seolbin An17Yeonkyung Kim18Younghui Kang19Byung Chul Kim20Jong Bhak21Jong Bhak22Jong Bhak23Jong Bhak24Eun-Seok Shin25Korean Genomics Center (KOGIC), Ulsan National Institute of Science and Technology (UNIST), Ulsan, Republic of KoreaClinomics Inc., Ulsan, Republic of KoreaClinomics Inc., Ulsan, Republic of KoreaKorean Genomics Center (KOGIC), Ulsan National Institute of Science and Technology (UNIST), Ulsan, Republic of KoreaDepartment of Biomedical Engineering, College of Information-Bio Convergence Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, Republic of KoreaClinomics Inc., Ulsan, Republic of KoreaClinomics Inc., Ulsan, Republic of KoreaClinomics Inc., Ulsan, Republic of KoreaDepartment of Mathematics, Kangwon National University, ChunCheon, Republic of KoreaKorean Genomics Center (KOGIC), Ulsan National Institute of Science and Technology (UNIST), Ulsan, Republic of KoreaDepartment of Biomedical Engineering, College of Information-Bio Convergence Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, Republic of KoreaDivision of Cardiology, Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University, Seoul, Republic of KoreaDivision of Cardiology, Department of Internal Medicine, Chung-Ang University College of Medicine, Chung-Ang University Gwangmyeong Hospital, Gwangmyeong, Republic of KoreaDepartment of Internal Medicine, Chungbuk National University Hospital, College of Medicine, Chungbuk National University, Cheongju, Republic of KoreaDepartment of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Republic of KoreaDepartment of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Republic of KoreaKorean Genomics Center (KOGIC), Ulsan National Institute of Science and Technology (UNIST), Ulsan, Republic of KoreaDepartment of Biomedical Engineering, College of Information-Bio Convergence Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, Republic of KoreaClinomics Inc., Ulsan, Republic of KoreaClinomics Inc., Ulsan, Republic of KoreaClinomics Inc., Ulsan, Republic of KoreaKorean Genomics Center (KOGIC), Ulsan National Institute of Science and Technology (UNIST), Ulsan, Republic of KoreaClinomics Inc., Ulsan, Republic of KoreaDepartment of Biomedical Engineering, College of Information-Bio Convergence Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, Republic of KoreaPersonal Genomics Institute (PGI), Genome Research Foundation (GRF), Osong, Republic of Korea0Department of Cardiology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of KoreaBackgroundAcute 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 methodsWe 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].ResultsOf 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.ConclusionOur 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.https://www.frontiersin.org/articles/10.3389/fcvm.2023.1226971/fullacute myocardial infarctiongenome-wide association studycardiac mortalitygenetic markerprognostic marker |
| spellingShingle | Yeonsu Jeon Yeonsu Jeon Sungwon Jeon Kyungwhan An Kyungwhan An Yeo Jin Kim Byoung-Chul Kim Hyojung Ryu Whan-Hyuk Choi HyunJoo Choi HyunJoo Choi Weon Kim Sang Yeub Lee Jang-Whan Bae Jin-Yong Hwang Min Gyu Kang Seolbin An Seolbin An Yeonkyung Kim Younghui Kang Byung Chul Kim Jong Bhak Jong Bhak Jong Bhak Jong Bhak Eun-Seok Shin Identification and validation of six acute myocardial infarction-associated variants, including a novel prognostic marker for cardiac mortality Frontiers in Cardiovascular Medicine acute myocardial infarction genome-wide association study cardiac mortality genetic marker prognostic marker |
| title | Identification and validation of six acute myocardial infarction-associated variants, including a novel prognostic marker for cardiac mortality |
| title_full | Identification and validation of six acute myocardial infarction-associated variants, including a novel prognostic marker for cardiac mortality |
| title_fullStr | Identification and validation of six acute myocardial infarction-associated variants, including a novel prognostic marker for cardiac mortality |
| title_full_unstemmed | Identification and validation of six acute myocardial infarction-associated variants, including a novel prognostic marker for cardiac mortality |
| title_short | Identification and validation of six acute myocardial infarction-associated variants, including a novel prognostic marker for cardiac mortality |
| title_sort | identification and validation of six acute myocardial infarction associated variants including a novel prognostic marker for cardiac mortality |
| topic | acute myocardial infarction genome-wide association study cardiac mortality genetic marker prognostic marker |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2023.1226971/full |
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