title: Investigation on genetic thrombophilic factors in FFPE autopsy tissue from subjects who died from pulmonary embolism.
abstract: Venous thromboembolism (VTE) is a multifactorial disease determined by a combination of inherited and acquired factors. Inherited factors include mutations in the genes coding for coagulation factors, some of which seem to exert a differential influence on the risk of developing deep vein thrombosis (DVT) and pulmonary embolism (PE). In post-mortem studies of subjects who have died from pulmonary embolism (PE), the analysis of the factors that may have augmented the VTE risk is often limited to acquired factors. This is due to the complexity-and sometimes the unfeasibility-of analyzing genetic factors and to insufficient knowledge of their individual roles in PE development. The present study used formalin-fixed paraffin-embedded (FFPE) tissue to investigate a panel of 12 polymorphisms-the largest ever studied-that affect the VTE risk. Tissue samples came from post-mortem examinations performed by the specialists of the Section of Legal Medicine of the Department of Pathology of Marche's Polytechnic University, and by the specialists of Health Care District Hospital of Imola, on 44 subjects who died from PE in the period 1997-2014. All individuals were found to have at least one mutation affecting the VTE risk. The present study demonstrates that genetic analysis can be performed post-mortem and the results are useful for forensic investigations, especially from MTHFR C677T and PAI-1 4G/5G polymorphisms. Broader studies using the techniques described herein are needed to determine the relative influence of the individual polymorphisms and their interaction in PE deaths.
authors.affiliation: Section of Legal Medicine, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Brandimarti
authors.affiliation: Section of Legal Medicine, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Alessandrini
authors.affiliation: Section of Legal Medicine, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Pesaresi
authors.affiliation: Section of Legal Medicine, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Catalani
authors.affiliation: Section of Legal Medicine, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: De Angelis
authors.affiliation: Clinical Laboratory & Molecular Diagnostics Department, INRCA-IRCCS, Ancona, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Galeazzi
authors.affiliation: Clinical Laboratory & Molecular Diagnostics Department, INRCA-IRCCS, Ancona, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Giovagnetti
authors.affiliation: Center of Epidemiology, Biostatistics and Medical Information Technology, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Gesuita
authors.affiliation: Department of Pathology, Health Care District Hospital of Imola, Imola, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Righi
authors.affiliation: Section of Legal Medicine, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Giorgetti
authors.affiliation: Section of Legal Medicine, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, Ancona, Italy. a.tagliabracci@univpm.it.
authors.forename: Adriano
authors.initials: A
authors.lastname: Tagliabracci
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005165:Factor V / Q000235:genetics; D005176:Factor XIII / Q000235:genetics; D005260:Female; D005340:Fibrinogen / Q000235:genetics; D005557:Formaldehyde; D020022:Genetic Predisposition to Disease; D005966:Glucuronidase / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008074:Lipoproteins / Q000235:genetics; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D016612:Paraffin Embedding; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011516:Prothrombin / Q000235:genetics; D011655:Pulmonary Embolism / Q000235:genetics*; D019851:Thrombophilia / Q000235:genetics*; D054556:Venous Thromboembolism / Q000235:genetics; D000099175:Heparanase
chemical_list: D005165:Factor V; D005176:Factor XIII; D005340:Fibrinogen; D005557:Formaldehyde; D005966:Glucuronidase; D008074:Lipoproteins; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D017395:Plasminogen Activator Inhibitor 1; D011516:Prothrombin; D000099175:Heparanase; C051321:SERPINE1 protein, human; C051928:lipoprotein-associated coagulation inhibitor; C573423:MTHFR protein, human
keywords: Deep vein thrombosis; Hereditary thrombophilia; Pulmonary embolism; Venous thromboembolism