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  • Title: Association of matrix metalloproteinase-1 and -3 promoter polymorphisms with clinical subsets of Norwegian primary sclerosing cholangitis patients.
    Author: Wiencke K, Louka AS, Spurkland A, Vatn M, Schrumpf E, Boberg KM, IBSEN Study Group.
    Journal: J Hepatol; 2004 Aug; 41(2):209-14. PubMed ID: 15288468.
    Abstract:
    BACKGROUND/AIMS: Primary sclerosing cholangitis (PSC) is considered an immune mediated liver disease of multifactorial and multigenetic aetiology. Concomitant ulcerative colitis (UC) is seen in many PSC patients, but the pathogenetic link between these disorders is unknown. Due to association with inflammation, fibrosis, and cancer development, the matrix metalloproteinases MMP-1 and MMP-3 are candidate genes for predisposition to both PSC, UC and cholangiocarcinoma. METHODS: We investigated the association of MMP-1 and MMP-3 promoter polymorphisms in 165 Norwegian PSC patients compared to 118 UC patients and 346 healthy controls. RESULTS: There were no differences in MMP-1 and MMP-3 frequencies between PSC patients and UC patients or healthy controls. PSC patients with UC showed an increased frequency of the MMP-3 allele 5A compared to PSC patients without UC (60% vs. 45%; P(c)=0.01). All patients (100%) with cholangiocarcinoma carried MMP-1 allele 1G, compared to only 72% of PSC patients without cholangiocarcinoma. CONCLUSIONS: We found no general associations of the MMP-1 and MMP-3 genes to PSC or UC among Norwegian patients, but specific alleles were associated to subsets of PSC patients with UC and cholangiocarcinoma. The results support the theory of genetic heterogeneity among PSC patients.
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