PMID- 21134112
OWN - NLM
STAT- MEDLINE
DCOM- 20111007
LR  - 20211020
IS  - 1478-3231 (Electronic)
IS  - 1478-3223 (Print)
IS  - 1478-3223 (Linking)
VI  - 31
IP  - 6
DP  - 2011 Jul
TI  - Genetic polymorphisms of matrix metalloproteinase 3 in primary sclerosing 
      cholangitis.
PG  - 785-91
LID - 10.1111/j.1478-3231.2010.02420.x [doi]
AB  - BACKGROUND: The damaging cholestasis inherent to primary sclerosing cholangitis 
      (PSC) results from bile duct stricturing because of progressive fibrosis. The 
      matrix metalloproteinase 3 (MMP3) degrades a wide range of matrix components and 
      is expressed by activated liver stellate cells, and so is a candidate for 
      involvement with the fibrotic processes underlying PSC. Moreover, the MMP3 gene 
      harbours polymorphisms associated with variation in its activity directly 
      impacting clinical phenotypes. AIMS: We aimed to examine the influence of MMP3 
      polymorphisms on PSC risk and progression. METHODS: Nine single nucleotide 
      polymorphisms (SNPs) tagging the common genetic variation of MMP3 were genotyped 
      in 266 PSC patients and 407 controls. SNPs and inferred haplotypes were assessed 
      for PSC association by logistic regression and score tests. The effect of SNPs on 
      survival to liver transplant or death was analysed using Cox regression, and 
      Kaplan-Meier curves were constructed. RESULTS: No association of PSC with 
      individual SNPs or haplotypes of MMP3 was detected. However, progression to death 
      or liver transplant was significantly associated with homozygosity for minor 
      alleles of rs522616, rs650108 and rs683878, particularly among PSC patients with 
      concurrent ulcerative colitis (UC) (strongest in redundant SNPs 
      rs650108/rs683878, hazard ratio=3.23, 95% confidence interval 1.45-7.25, 
      P=0.004). CONCLUSIONS: Genetic variation in MMP3 influences PSC progression, 
      possibly in the context of coexisting UC. While the functional variants and 
      specific mechanisms remain unknown, this finding implicates the turnover of the 
      extracellular matrix as an important and variable component of PSC pathogenesis. 
      Efforts to understand this process could form the basis for developing effective 
      treatments, which are currently lacking for PSC.
CI  - (c) 2010 John Wiley & Sons A/S.
FAU - Juran, Brian D
AU  - Juran BD
AD  - Center for Basic Research in Digestive Diseases, Division of Gastroenterology and 
      Hepatology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
FAU - Atkinson, Elizabeth J
AU  - Atkinson EJ
FAU - Schlicht, Erik M
AU  - Schlicht EM
FAU - Larson, Joseph J
AU  - Larson JJ
FAU - Ellinghaus, David
AU  - Ellinghaus D
FAU - Franke, Andre
AU  - Franke A
FAU - Lazaridis, Konstantinos N
AU  - Lazaridis KN
LA  - eng
GR  - R01 DK084960/DK/NIDDK NIH HHS/United States
GR  - R01 DK084960-01A1/DK/NIDDK NIH HHS/United States
GR  - R01DK084960/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20101207
PL  - United States
TA  - Liver Int
JT  - Liver international : official journal of the International Association for the 
      Study of the Liver
JID - 101160857
RN  - EC 3.4.24.17 (MMP3 protein, human)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
CIN - Liver Int. 2011 Jul;31(6):751-4. PMID: 21645205
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Case-Control Studies
MH  - Child
MH  - Cholangitis, Sclerosing/enzymology/*genetics/mortality
MH  - Colitis, Ulcerative/epidemiology
MH  - Comorbidity
MH  - Disease Progression
MH  - Female
MH  - Gene Frequency
MH  - Genetic Association Studies
MH  - Genetic Predisposition to Disease
MH  - Haplotypes
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Linkage Disequilibrium
MH  - Logistic Models
MH  - Male
MH  - Matrix Metalloproteinase 3/*genetics
MH  - Middle Aged
MH  - Minnesota
MH  - Phenotype
MH  - *Polymorphism, Single Nucleotide
MH  - Proportional Hazards Models
MH  - Risk Assessment
MH  - Risk Factors
MH  - Young Adult
PMC - PMC3139245
MID - NIHMS310300
EDAT- 2010/12/08 06:00
MHDA- 2011/10/08 06:00
PMCR- 2011/07/19
CRDT- 2010/12/08 06:00
PHST- 2010/12/08 06:00 [entrez]
PHST- 2010/12/08 06:00 [pubmed]
PHST- 2011/10/08 06:00 [medline]
PHST- 2011/07/19 00:00 [pmc-release]
AID - 10.1111/j.1478-3231.2010.02420.x [doi]
PST - ppublish
SO  - Liver Int. 2011 Jul;31(6):785-91. doi: 10.1111/j.1478-3231.2010.02420.x. Epub 
      2010 Dec 7.