Effect of a thrombin receptor (protease‐activated receptor 1, PAR‐1) gene polymorphism in chronic hepatitis C liver fibrosis

Abstract

In conclusion, these findings suggest that PAR-1 receptor polymorphisms influence the progression of liver fibrosis.

The SOD2 C47T polymorphism influences NAFLD fibrosis severity: Evidence from case-control and intra-familial allele association studies

“…As with many other complex genetic diseases, susceptibility to fibrotic NAFLD is likely to be determined by epistatic interaction of a number of different genes and environmental influences, indeed several genetic modifiers have been reported across a range of progressive liver diseases [5,34,[47][48][49][50][51][52][53]. In clinical studies, it is difficult or impossible to control for all subtle interpatient variations, whether genetic or environmental, that interact to determine disease phenotype and progression [7] and so there remains a need for validation in independent patient cohorts, either through further candidate gene studies or largescale genome-wide association studies.…”

Prothrombotic genetic risk factors are associated with an increased risk of liver fibrosis in the general population

“…The exact mechanism of this influence has not yet been fully elucidated, but thrombin seems to play a key role. Thrombin could cause liver fibrosis by directly activating hepatic stellate cells by binding the protease-activated receptor 1 [2][3][4][5]. An alternative hypothesis describes that thrombin production causes the formation of occlusive thrombi which eventually results in tissue ischemia, parenchymal extinction and ultimately liver fibrosis and cirrhosis [6,7].…”

Uncoupling of the profibrotic and hemostatic effects of thrombin in lung fibrosis

“…This dissociation of the role of thrombin activity from hemostasis has important and immediate clinical implications for individuals with IPF, given recent findings that warfarin treatment is not beneficial in IPF (32), and the clinical availability of direct thrombin inhibitors that our data suggest could benefit these patients. In addition, these findings may have widespread relevance for pathological fibrosis, as the thrombin/PAR1/α v β 6 /TGF-β axis has also been implicated in the development of fibrosis in other organ systems, including the liver and kidneys (33)(34)(35)(36)(37)(38).…”