Functional analysis of an unusual length polymorphism in the human antithrombin III (AT3) gene promoter
| Autor: | Michael Krawczak, Lutz-Peter Berg, V. V. Kakkar, David Neil Cooper, David Stuart Millar, Winter Pc, Deborah A. Scopes, Mayne Ee |
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| Rok vydání: | 1995 |
| Předmět: |
Carcinoma
Hepatocellular Recombinant Fusion Proteins Antithrombin III Molecular Sequence Data Population Sequence Homology Biology Transfection Homology (biology) Liver Neoplasms Experimental Genotype Tumor Cells Cultured medicine Animals Humans Allele Luciferases Promoter Regions Genetic education Gene Alleles Genetics education.field_of_study Polymorphism Genetic Base Sequence Antithrombin Promoter Hematology General Medicine Blotting Northern Molecular biology Phenotype DNA Probes Ireland medicine.drug |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 0957-5235 |
| Popis: | The prevalence of the alternative alleles of an unusual length polymorphism in the promoter of the human antithrombin III (AT3) gene was determined in a sample of 155 unrelated individuals from the Northern Irish population. The 108bp L allele and the 32bp S allele occurred at frequencies of 0.21 and 0.79 respectively. Some homology was noted between the L-specific sequence and the region immediately downstream. Residual homology was also evident between the L and S sequences, suggesting that the S allele was derived from the L allele during evolution by partial deletion followed by sequence divergence. The functional significance of the polymorphism was investigated by transient transfection of AT3 promoter/luciferase reporter gene constructs into two human hepatoma cell lines in vitro. The promoter strength of the L allele was found to be 1.6-fold higher than the S allele in HepG2 cells whereas in Hep3B cells, the strength of the S allele was 1.7-fold higher than that of the L allele. In order to evaluate the phenotypic consequences of the AT3 promoter polymorphism in vivo, plasma samples from the 155 control individuals were assayed for antithrombin III (ATIII) activity. Mean activities of the different promoter polymorphism genotypes (SS, LL, SL) were not significantly different. These results suggest that the AT3 promoter polymorphism does not contribute to the variation in plasma ATIII activity that occurs in the general population. |
| Databáze: | OpenAIRE |
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