title: 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.affiliation: Institute of Clinical Pharmacology, University of Berne, Switzerland. felix.stickel@ikp.unibe.ch
authors.forename: Felix
authors.initials: F
authors.lastname: Stickel
authors.forename: Christoph H
authors.initials: CH
authors.lastname: Osterreicher
authors.forename: Juliane
authors.initials: J
authors.lastname: Halangk
authors.forename: Thomas
authors.initials: T
authors.lastname: Berg
authors.forename: Nils
authors.initials: N
authors.lastname: Homann
authors.forename: Claus
authors.initials: C
authors.lastname: Hellerbrand
authors.forename: Eleonora
authors.initials: E
authors.lastname: Patsenker
authors.forename: Vreni
authors.initials: V
authors.lastname: Schneider
authors.forename: Armin
authors.initials: A
authors.lastname: Kolb
authors.forename: Helmut
authors.initials: H
authors.lastname: Friess
authors.forename: Detlef
authors.initials: D
authors.lastname: Schuppan
authors.forename: Gero
authors.initials: G
authors.lastname: Puhl
authors.forename: Helmut K
authors.initials: HK
authors.lastname: Seitz
authors.forename: Julian L B
authors.initials: JL
authors.lastname: Leathart
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Day
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D005858:Germany; D006801:Humans; D008099:Liver / Q000201:enzymology; D008104:Liver Cirrhosis, Alcoholic / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D006113:United Kingdom
chemical_list: D012333:RNA, Messenger; D019278:Matrix Metalloproteinase 3