期刊
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
卷 23, 期 9, 页码 1403-1409出版社
WILEY
DOI: 10.1111/j.1440-1746.2007.05220.x
关键词
coagulation; fibrogenesis; liver injury; stellate cells; thrombin receptor
资金
- MRC Clinical Research
- VIRGIL European Network of Excellence on Antiviral Drug Resistance [LSHM-CT2004- 503359]
- Medical Research Council [G84/6233] Funding Source: researchfish
- National Institute for Health Research [CL-2007-21-007] Funding Source: researchfish
- MRC [G84/6233] Funding Source: UKRI
Background and Aim: Tissue injury leads to activation of coagulation and generation of thrombin. Inhibition of thrombin receptor protease-activated receptor 1 (PAR-1) has been shown to reduce liver fibrosis in animals. This study aimed to evaluate the effect of PAR-1 gene polymorphism on rate of liver fibrosis (RF) in chronic hepatitis C. Methods: Polymorphisms studied: C > T transition 1426 bp upstream of translation start site (-1426C/T), 13 bp repeat of preceding -506 5'-CGGCCGCGGGAAG-3' sequence (-506I/D), and A > T transversion in intervening sequence (IVS) 14 bp upstream of exon-2 start site (IVS-14A/T). A total of 287 European and 90 Brazilian patients were studied. Results: 1426C/T polymorphism: There was a trend to higher RF in patients with the TT genotype (P = 0.06) and an association between genotype CC and slow fibrosis (P = 0.03) in Europeans. In males, RF was significantly higher in those with the TT genotype compared to CT (P = 0.003) and CC (P = 0.007). There was a significant association between TT and fast fibrosis (P = 0.04). This was confirmed in an independent cohort of Brazilians where RF was higher in TT than in CC (P = 0.03). Analysis of -506I/D showed no difference in RF and distribution of slow/fast fibrosis among different genotypes in both populations. Analysis of IVS-14A/T showed no difference between genotypes. Conclusion: In conclusion, these findings suggest that PAR-1 receptor polymorphisms influence the progression of liver fibrosis.
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