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MMP ‐2 is a disease‐modifying gene in primary sclerosing cholangitis
Author(s) -
Sebib Korkmaz Kerem,
Rooij BertJan F.,
Hoek Bart,
Janse Marcel,
Coenraad Minneke J.,
Reijden Johan J.,
Weersma Rinse K.,
Porte Robert J.,
Voorneveld Philip W.,
Baranski Andrzej G.,
Verspaget Hein W.
Publication year - 2014
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12237
Subject(s) - genotype , medicine , primary sclerosing cholangitis , gastroenterology , hazard ratio , allele , liver transplantation , matrix metalloproteinase , inflammatory bowel disease , gene polymorphism , disease , transplantation , gene , biology , confidence interval , genetics
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 ( MMP s) 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 , CI s 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.