MMP-2 is a disease-modifying gene in primary sclerosing cholangitis
Article first published online: 28 JUN 2013
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Volume 34, Issue 2, pages 274–280, February 2014
How to Cite
Liver Int. 2014: 34:274–280
- Issue published online: 7 JAN 2014
- Article first published online: 28 JUN 2013
- Accepted manuscript online: 4 JUN 2013 12:53AM EST
- Manuscript Accepted: 26 MAY 2013
- Manuscript Received: 8 JAN 2013
- matrix metalloproteinase;
- orthotopic liver transplantation;
- primary sclerosing cholangitis
Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of the bile ducts, frequently necessitating orthotopic liver transplantation (OLT), often accompanied by inflammatory bowel disease (IBD). Matrix metalloproteinases (MMPs) are associated with fibrotic diseases caused by the involvement in tissue remodelling.
To evaluate the contribution of MMP-2 and -9 promoter polymorphisms to disease severity in PSC, as assessed by death or need for OLT.
Matrix metalloproteinase-2 (−1306 C/T) and -9 (−1562 C/T) gene promoter polymorphisms were analyzed in 132 PSC patients. Follow-up was from onset PSC until death, OLT or end of follow-up.
Twenty-year cumulative incidence (CI) of death or OLT for PSC patients with MMP-2 CT genotype was 86.5% compared to 52.8% for CC genotype (P = 0.030) and reached 100% at 11.3 years for TT genotype. In patients with IBD, CIs were similar: 20-years CI of death or OLT for MMP-2 CT genotype was 86.0% compared to 49.0% for CC genotype and 100% at 11.3 years for TT genotype. Patients without IBD showed a similar trend in 20 years CI for MMP-2 CT (77.8%) compared to CC (57.8%) and CI for TT genotype reached 100% at 9.3 years. Multivariate analysis showed, along with age at diagnosis, a stepwise increase in hazard ratio for MMP-2 T-allele polymorphism for death or OLT. MMP-9 genotype was not associated with disease severity in PSC.
Matrix metalloproteinase-2 C to T-1306 gene promoter polymorphism in PSC is an independent risk factor for disease severity as reflected by the need for OLT or disease progression leading to mortality.