Beck Hans Christian, Skovgaard Asmus Cosmos, Mohammadnejad Afsaneh, Palstrøm Nicolai Bjødstrup, Nielsen Palle Fruekilde, Mengel-From Jonas, Hjelmborg Jacob, Rasmussen Lars Melholt, Soerensen Mette
Center for Individualized Medicine in Arterial Diseases, Department of Clinical Biochemistry, Odense University Hospital, J. B. Winsloews Vej 4, 5000 Odense, Denmark.
The Danish Twin Registry and Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark.
Int J Mol Sci. 2024 Feb 24;25(5):2638. doi: 10.3390/ijms25052638.
Acute myocardial infarction (AMI) is a major cause of mortality and morbidity worldwide, yet biomarkers for AMI in the short- or medium-term are lacking. We apply the discordant twin pair design, reducing genetic and environmental confounding, by linking nationwide registry data on AMI diagnoses to a survey of 12,349 twins, thereby identifying 39 twin pairs (48-79 years) discordant for their first-ever AMI within three years after blood sampling. Mass spectrometry of blood plasma identified 715 proteins. Among 363 proteins with a call rate > 50%, imputation and stratified Cox regression analysis revealed seven significant proteins (FDR < 0.05): FGD6, MCAM, and PIK3CB reflected an increased level in AMI twins relative to their non-AMI co-twins (HR > 1), while LBP, IGHV3-15, C1RL, and APOC4 reflected a decreased level in AMI twins relative to their non-AMI co-twins (HR < 1). Additional 50 proteins were nominally significant ( < 0.05), and bioinformatics analyses of all 57 proteins revealed biology within hemostasis, coagulation cascades, the immune system, and the extracellular matrix. A protein-protein-interaction network revealed Fibronectin 1 as a central hub. Finally, technical validation confirmed MCAM, LBP, C1RL, and APOC3. We put forward novel biomarkers for incident AMI, a part of the proteome field where markers are surprisingly rare and where additional studies are highly needed.
急性心肌梗死（AMI）是全球范围内导致死亡和发病的主要原因，然而，目前缺乏用于短期或中期诊断AMI的生物标志物。我们采用不一致双胞胎对设计，通过将全国范围内的AMI诊断登记数据与一项针对12349对双胞胎的调查相联系，减少遗传和环境混杂因素，从而识别出39对（年龄在48 - 79岁之间）在采血后三年内首次发生AMI情况不一致的双胞胎。血浆质谱分析鉴定出715种蛋白质。在检出率>50%的363种蛋白质中，插补和分层Cox回归分析揭示了7种显著蛋白质（FDR<0.05）：FGD6、MCAM和PIK3CB在AMI双胞胎中相对于其非AMI的同卵双胞胎水平升高（HR>1），而LBP、IGHV3 - 15、C1RL和APOC4在AMI双胞胎中相对于其非AMI的同卵双胞胎水平降低（HR<1）。另外50种蛋白质具有名义显著性（<0.05），对所有57种蛋白质的生物信息学分析揭示了止血、凝血级联反应、免疫系统和细胞外基质方面的生物学特性。蛋白质 - 蛋白质相互作用网络显示纤连蛋白1是一个中心枢纽。最后，技术验证证实了MCAM、LBP、C1RL和APOC3。我们提出了用于新发AMI的新型生物标志物，在蛋白质组领域这一部分，标志物出奇地稀少，非常需要进一步的研究。
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