The GEnetic Syntax Score: a genetic risk assessment implementation tool grading the complexity of coronary artery disease—rationale and design of the GESS study

BMC Cardiovascular Disorders

Anastasios Kartas¹  Georgios Sianos¹  Christos Stefopoulos¹  Andreas S. Papazoglou¹  Nikolaos Stalikas¹  Ηaralambos Karvounis¹  Efstratios Karagiannidis¹  Georgios Sofidis¹  Nikolaos Mittas²  Eleftherios Angelis³  Eleni Mezarli⁴  Aggeliki Lampri⁴  Anna Pappa-Konidari⁵  Fani Chatzopoulou⁵  Dimitrios Chatzidimitriou⁵  Nikoleta F. Theodoroula⁶  Konstantinos A. Kyritsis⁶  Ioannis S. Vizirianakis⁶ 

[1] Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki;Department of Chemistry, International Hellenic University;Department of Informatics, Aristotle University of Thessaloniki;Labnet Laboratories;Laboratory of Microbiology, School of Medicine, Aristotle University of Thessaloniki;Laboratory of Pharmacology, School of Pharmacy, Aristotle University of Thessaloniki;

关键词: Genetics;    Pharmacogenomics;    SNPs;    NGS;    Biomarkers;    Coronary artery disease;   

DOI  :  10.1186/s12872-021-02092-5

来源: DOAJ

【 摘 要 】

Abstract Background Coronary artery disease (CAD) remains one of the leading causes of mortality worldwide and is associated with multiple inherited and environmental risk factors. This study is designed to identify, design, and develop a panel of genetic markers that combined with clinical and angiographic information, will facilitate the creation of a personalized risk prediction algorithm (GEnetic Syntax Score—GESS). GESS score could be a reliable tool for predicting cardiovascular risk for future adverse events and for guiding therapeutic strategies. Methods GESS (ClinicalTrials.gov Identifier: NCT03150680) is a prospective, non-interventional clinical study designed to enroll 1080 consecutive patients with no prior history of coronary revascularization procedure, who undergo scheduled or emergency coronary angiography in AHEPA, University General Hospital of Thessaloniki. Next generation sequencing (NGS) technology will be used to genotype specific single-nucleotide polymorphisms (SNPs) across the genome of study participants, which were identified as clinically relevant to CAD after extensive bioinformatic analysis of literature-based SNPs. Enrichment analyses of Gene Ontology-Molecular Function, Reactome Pathways and Disease Ontology terms were also performed to identify the top 15 statistically significant terms and pathways. Furthermore, the SYNTAX score will be calculated for the assessment of CAD severity of all patients based on their angiographic findings. All patients will be followed-up for one-year, in order to record any major adverse cardiovascular events. Discussion A group of 228 SNPs was identified through bioinformatic and pharmacogenomic analysis to be involved in CAD through a wide range of pathways and was correlated with various laboratory and clinical parameters, along with the patients' response to clopidogrel and statin therapy. The annotation of these SNPs revealed 127 genes being affected by the presence of one or more SNPs. The first patient was enrolled in the study in February 2019 and enrollment is expected to be completed until June 2021. Hence, GESS is the first trial to date aspiring to develop a novel risk prediction algorithm, the GEnetic Syntax Score, able to identify patients at high risk for complex CAD based on their molecular signature profile and ultimately promote pharmacogenomics and precision medicine in routine clinical settings. Trial registration GESS trial registration: ClinicalTrials.gov Number: NCT03150680. Registered 12 May 2017- Prospectively registered, https://clinicaltrials.gov/ct2/show/NCT03150680 .

【 授权许可】

Unknown