No role of matrixmetalloproteinase-3 genetic promoter polymorphism 1171 as a risk factor for cirrhosis in alcoholic liver disease

Felix Stickel, Christoph H. Österreicher, Juliane Halangk, Thomas Berg, Nils Homann, Claus Hellerbrand, Eleonora Patsenker, Vreni Schneider, Armin Kolb, Helmut Friess, Detlef Schuppan, Gero Puhl, Helmut K. Seitz, Julian L.B. Leathart, Christopher P. Day

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Background: As only a minority of alcoholics develop cirrhosis, polymorphic genes, whose products are involved in fibrosis development were suggested to confer individual susceptibility. We tested whether a functional promoter polymorphism in the gene encoding matrix metalloproteinase-3 (MMP-3; 1171 5A/6A) was associated liver cirrhosis in alcoholics. Methods: Independent cohorts from the UK and Germany were studied. (i) UK cohort: 320 alcoholic cirrhotics and 183 heavy drinkers without liver damage and (ii) German cohort: 149 alcoholic cirrhotics, 220 alcoholic cirrhotics who underwent liver transplantation and 151 alcoholics without liver disease. Patients were genotyped for MMP-3 variants by restriction fragment length polymorphism, single strand confirmation polymorphism, and direct sequencing. In addition, MMP-3 transcript levels were correlated with MMP-3 genotype in normal liver tissues. Results: Matrix metalloproteinase-3 genotype and allele distribution in all 1023 alcoholic patients were in Hardy-Weinberg equilibrium. No significant differences in MMP-3 genotype and allele frequencies were observed either between alcoholics with or without cirrhosis. There were no differences in hepatic mRNA transcription levels according to MMP-3 genotype. Conclusions: Matrix metalloproteinase-3 1171 promoter polymorphism plays no role in the genetic predisposition for liver cirrhosis in alcoholics. Stringently designed candidate gene association studies are required to exclude chance observations.

Original languageEnglish
Pages (from-to)959-965
Number of pages7
JournalAlcoholism: Clinical and Experimental Research
Volume32
Issue number6
DOIs
StatePublished - Jun 2008
Externally publishedYes

Keywords

  • Alcoholic Liver Disease
  • Cirrhosis
  • Genetic Risk
  • Matrixmetalloproteinase-3 Polymorphism

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