MMP-2 is a disease-modifying gene in primary sclerosing cholangitis.

Background 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. Aim To evaluate the contribution of MMP-2 and -9 promoter polymorphisms to disease severity in PSC, as assessed by death or need for OLT. Methods 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. Results 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. Conclusion 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. [ABSTRACT FROM AUTHOR]