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

• Published in: Gene Vol. 568; no. 1; pp. 85 - 88
• Main Authors: D'Amico, Mario, Pasta, Francesca, Pasta, Linda
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.08.2015
• Subjects: Alcohol Drinking - adverse effects; Alcoholic cirrhosis; Cirrhosis; Cryptogenic liver cirrhosis; European Continental Ancestry Group; Female; Genetic Association Studies; Genetic mutation; Genetic Predisposition to Disease; HBV; HCV; Hepatitis B virus; Hepatitis C virus; Humans; Liver; Liver Cirrhosis - congenital; Liver Cirrhosis - genetics; Liver fibrosis; Male; Methylenetetrahydrofolate reductase; Methylenetetrahydrofolate Reductase (NADPH2) - genetics; MTHFR; MTHFR C677T; PAI-1; Plasminogen Activator Inhibitor 1 - genetics; Plasminogen activator inhibitor-type 1; Polymorphism, Single Nucleotide; Portal Vein - pathology; Portal vein thrombosis; Prothrombin 20210A; Prothrombin gene; Risk Factors; Thrombophilia; V Leiden 506Q; Venous Thrombosis - genetics; THRGFs; Alcoholic cirrhosis; Prothrombin gene; Liver; HCC; MTHFR; Methylenetetrahydrofolate reductase; V Leiden 506Q; Liver fibrosis; Genetic mutation; Portal vein thrombosis; PVT; Prothrombin 20210A; Thrombophilia; Cirrhosis; Plasminogen activator inhibitor-type 1; Cryptogenic liver cirrhosis; PAI-1; MTHFR C677T; HCV; HBV
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2015.05.034

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. •Genetic thrombophilia in 339/865 liver cirrhosis patients; 243 of them with PVT•PAI1 4G-4G or MTHFR 677TT increases 2–5 fold the risk of no virus cirrhosis and PVT.•Pivotal role of PAI-1 4G-4G and MTHFR 677TT in thrombo-fibrogenetic mechanisms•PAI-1 4G-4G and MTHFR 677TT screening in alcohol, cryptogenic cirrhosis patients•The need of new therapies for lowering the activity of hepatic stellate cells