PMID- 18445105
OWN - NLM
STAT- MEDLINE
DCOM- 20080701
LR  - 20161124
IS  - 1530-0277 (Electronic)
IS  - 0145-6008 (Linking)
VI  - 32
IP  - 6
DP  - 2008 Jun
TI  - No role of matrixmetalloproteinase-3 genetic promoter polymorphism 1171 as a risk 
      factor for cirrhosis in alcoholic liver disease.
PG  - 959-65
LID - 10.1111/j.1530-0277.2008.00654.x [doi]
AB  - 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.
FAU - Stickel, Felix
AU  - Stickel F
AD  - Institute of Clinical Pharmacology, University of Berne, Switzerland. 
      felix.stickel@ikp.unibe.ch
FAU - Osterreicher, Christoph H
AU  - Osterreicher CH
FAU - Halangk, Juliane
AU  - Halangk J
FAU - Berg, Thomas
AU  - Berg T
FAU - Homann, Nils
AU  - Homann N
FAU - Hellerbrand, Claus
AU  - Hellerbrand C
FAU - Patsenker, Eleonora
AU  - Patsenker E
FAU - Schneider, Vreni
AU  - Schneider V
FAU - Kolb, Armin
AU  - Kolb A
FAU - Friess, Helmut
AU  - Friess H
FAU - Schuppan, Detlef
AU  - Schuppan D
FAU - Puhl, Gero
AU  - Puhl G
FAU - Seitz, Helmut K
AU  - Seitz HK
FAU - Leathart, Julian L B
AU  - Leathart JL
FAU - Day, Christopher P
AU  - Day CP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080426
PL  - England
TA  - Alcohol Clin Exp Res
JT  - Alcoholism, clinical and experimental research
JID - 7707242
RN  - 0 (RNA, Messenger)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Adult
MH  - Analysis of Variance
MH  - Cohort Studies
MH  - Female
MH  - Gene Frequency
MH  - Genetic Predisposition to Disease/*genetics
MH  - Genotype
MH  - Germany
MH  - Humans
MH  - Liver/enzymology
MH  - Liver Cirrhosis, Alcoholic/*genetics
MH  - Logistic Models
MH  - Male
MH  - Matrix Metalloproteinase 3/*genetics
MH  - Middle Aged
MH  - Polymorphism, Genetic/*genetics
MH  - Polymorphism, Restriction Fragment Length
MH  - Promoter Regions, Genetic/*genetics
MH  - RNA, Messenger/analysis
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - United Kingdom
EDAT- 2008/05/01 09:00
MHDA- 2008/07/02 09:00
CRDT- 2008/05/01 09:00
PHST- 2008/05/01 09:00 [pubmed]
PHST- 2008/07/02 09:00 [medline]
PHST- 2008/05/01 09:00 [entrez]
AID - ACER654 [pii]
AID - 10.1111/j.1530-0277.2008.00654.x [doi]
PST - ppublish
SO  - Alcohol Clin Exp Res. 2008 Jun;32(6):959-65. doi: 
      10.1111/j.1530-0277.2008.00654.x. Epub 2008 Apr 26.