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

Stickel, Felix; Osterreicher, Christoph H; Halangk, Juliane; Berg, Thomas; Homann, Nils; Hellerbrand, Claus; Patsenker, Eleonora; Schneider, Vreni; Kolb, Armin; Friess, Helmut; Schuppan, Detlef; Puhl, Gero; Seitz, Helmut K; Leathart, Julian L B; Day, Christopher P (2008). No role of matrixmetalloproteinase-3 genetic promoter polymorphism 1171 as a risk factor for cirrhosis in alcoholic liver disease. Alcoholism: clinical and experimental research, 32(6), pp. 959-65. Oxford: Wiley-Blackwell 10.1111/j.1530-0277.2008.00654.x

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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.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology 04 Faculty of Medicine > Service Sector > Institute of Clinical Pharmacology and Visceral Research [discontinued]
UniBE Contributor:	Stickel, Felix, Patsenker, Eleanora, Schneider, Vreni
ISSN:	0145-6008
ISBN:	18445105
Publisher:	Wiley-Blackwell
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 15:05
Last Modified:	05 Dec 2022 14:20
Publisher DOI:	10.1111/j.1530-0277.2008.00654.x
PubMed ID:	18445105
Web of Science ID:	000256116600007
URI:	https://boris.unibe.ch/id/eprint/28353 (FactScience: 120255)