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No Role of Matrixmetalloproteinase‐3 Genetic Promoter Polymorphism 1171 as a Risk Factor for Cirrhosis in Alcoholic Liver Disease
Author(s) -
Stickel Felix,
Österreicher Christoph H.,
Halangk Juliane,
Berg Thomas,
Homann Nils,
Hellerbrand Claus,
Patsenker Eleonora,
Schneider Vreni,
Kolb Armin,
Friess Helmut,
Schuppan Detlef,
Puhl Gero,
Seitz Helmut K.,
Leathart Julian L. B.,
Day Christopher P.
Publication year - 2008
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2008.00654.x
Subject(s) - cirrhosis , alcoholic liver disease , genotype , gastroenterology , allele , liver disease , medicine , biology , restriction fragment length polymorphism , genetics , gene
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.