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

Alcohol Clin Exp Res. 2008 Jun;32(6):959-65. doi: 10.1111/j.1530-0277.2008.00654.x. Epub 2008 Apr 26.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • RNA, Messenger
  • Matrix Metalloproteinase 3