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

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.

Zur Geschichte der Blutbeschuldigungen gegen die Juden im Mittelalter und in der Neuzeit (1171-1883) : nach d. Quellen dargest.

von M. H. Friedländer

Na 50 Nachlass Arthur Schopenhauer - 'Schopenhauer-Archiv', 1171 - Verarbeitung der väterlichen Erinnerungen an Schopenhauer

abgedruckt in: Schopenhauer-Jahrbuch 39 (1958), S. 127 (Teilabdruck)

Foraminiferal study of ODP Hole 189-1171

Sequence boundary ages determined in shallow-water sediments obtained from ODP (Ocean Drilling Program) Leg 189 Site 1171 (South Tasman Rise) compare well with other stratigraphic records (New Jersey, United States, and northwestern Europe) and d18O increases from deep-sea records, indicating that significant (>10 m) eustatic changes occurred during the early to middle Eocene (51-42 Ma). Sequence boundaries were identified and dated using lithology, bio- and magnetostratigraphy, water-depth changes, CaCO3 content, and physical properties (e.g., photospectrometry). They are characterized by a sharp bioturbated surface, low CaCO3 content, and an abrupt increase in glauconite above the surface. Foraminiferal biofacies and planktonic/benthic foraminiferal ratios were used to estimate water-depth changes. Ages of six sequence boundaries (50.9, 49.2, 48.5-47.8, 47.1, 44.5, and 42.6 Ma) from Site 1171 correlate well to the timings of d18O increases and sequence boundaries identified from other Eocene studies. The synchronous nature of sequence boundary development from globally distal sites and d18O increases indicates a global control and that glacioeustasy was operating in this supposedly ice-free world. This is supported by previous modeling studies and atmospheric pCO2 estimates showing that the first time pCO2 levels decreased below a threshold that would support the development of an Antarctic ice sheet occurred at ca. 51 Ma. Estimates of sea-level amplitudes range from ~20 m for the early Eocene (51-49 Ma) and ~25 m to ~45 m for the middle Eocene (48-42 Ma) using constraints established for Oligocene d18O records.