title: Thrombophilic genetic factors PAI-1 4G-4G and MTHFR 677TT as risk factors of alcohol, cryptogenic liver cirrhosis and portal vein thrombosis, in a Caucasian population.
abstract: The thrombophilic genetic factors (THRGFs), PAI-1 4G-4G, MTHFR 677TT, V Leiden 506Q and Prothrombin 20210A, were studied as risk factors in 865 Caucasian patients with liver cirrhosis, consecutively enrolled from June 2008 to January 2014. A total of 582 HCV, 80 HBV, 94 alcohol, (82 with more than one etiologic factor) and 191 cryptogenic patients with liver cirrhosis had been consecutively enrolled; 243 patients showed portal vein thrombosis (PVT). At least one of the above THRGFs was present in 339/865 patients (39.2%). PAI-1 4G-4G and MTHFR 677TT were the most frequent THRGFs, statistically significant in patients with alcohol, cryptogenic liver cirrhosis, and PVT: respectively 24 and 28, 50 and 73, and 65 and 83 (all chi-square tests>3.84, and p values<0.05). Two logistic regression analysis, using PAI-1 4G-4G and MTHFR 677TT, as dependent variable, confirmed the independent significant relationship of these THRGFs with alcohol, cryptogenic liver cirrhosis and PVT. PAI 1 and MTHFR 677 genotypes, deviated from those expected in populations in Hardy-Weinberg equilibrium (all p values<0.05), in the subgroups of patients with alcohol, cryptogenic liver cirrhosis and presence of PVT. Our study shows the pivotal role of PAI-1 4G-4G and MTHFR 677TT in patients with alcohol, cryptogenic liver cirrhosis, and PVT, in a Caucasian population. In conclusion, thrombo and fibro-genetic mechanisms of PAI-1 4G-4G and MTHFR 677TT, could have a role in the development of liver cirrhosis, mainly in patients without HCV and HBV, and PVT.
authors.affiliation: Department of Biopathology and Medical and Forensic Biotechnologies and Biomedical, University of Palermo, Via del Vespro 127, 90127, Italy. Electronic address: damicoma@gmail.com.
authors.forename: Mario
authors.initials: M
authors.lastname: D'Amico
authors.affiliation: Department of Medicine, Clinica Candela, Via Villareale 54, 90141 Palermo, Italy. Electronic address: francescapa88@yahoo.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Pasta
authors.affiliation: Department of Medicine, Clinica Candela, Via Villareale 54, 90141 Palermo, Italy; Ospedale Cervello, AOOR Villa Sofia Cervello, Via Trabucco 180, 90146 Palermo, Italy. Electronic address: lindpas@yahoo.it.
authors.forename: Linda
authors.initials: L
authors.lastname: Pasta
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008103:Liver Cirrhosis / Q000151:congenital* / Q000235:genetics; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011169:Portal Vein / Q000473:pathology*; D012307:Risk Factors; D020246:Venous Thrombosis / Q000235:genetics*; D044465:White People
chemical_list: D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
keywords: Alcoholic cirrhosis; Cirrhosis; Cryptogenic liver cirrhosis; Genetic mutation; HBV; HCV; Liver; Liver fibrosis; MTHFR; MTHFR C677T; Methylenetetrahydrofolate reductase; PAI-1; Plasminogen activator inhibitor-type 1; Portal vein thrombosis; Prothrombin 20210A; Prothrombin gene; Thrombophilia; V Leiden 506Q