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

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.

• Authors: Felix Stickel, Christoph H Osterreicher, 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
• Journal: Alcoholism, clinical and experimental research (Alcohol Clin Exp Res) Vol. 32 Issue 6 Pg. 959-65 (Jun 2008) ISSN: 1530-0277 [Electronic] England
• PMID: 18445105 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Messenger
• Matrix Metalloproteinase 3

Topics

• Adult
• Analysis of Variance
• Cohort Studies
• Female
• Gene Frequency
• Genetic Predisposition to Disease (genetics)
• Genotype
• Germany
• Humans
• Liver (enzymology)
• Liver Cirrhosis, Alcoholic (genetics)
• Logistic Models
• Male
• Matrix Metalloproteinase 3 (genetics)
• Middle Aged
• Polymorphism, Genetic (genetics)
• Polymorphism, Restriction Fragment Length
• Promoter Regions, Genetic (genetics)
• RNA, Messenger (analysis)
• Reverse Transcriptase Polymerase Chain Reaction
• United Kingdom