Mechanistic role of a disease-associated genetic variant within the ADAM33 asthma susceptibility gene
| العنوان: | Mechanistic role of a disease-associated genetic variant within the ADAM33 asthma susceptibility gene |
|---|---|
| المؤلفون: | Randall David Little, Heidi Giese, Richard G. Del Mastro, Laura Turenne, Tim Keith, Paul Van Eerdewegh, Klaus J W May |
| المصدر: | BMC Medical Genetics BMC Medical Genetics, Vol 8, Iss 1, p 46 (2007) |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | lcsh:Internal medicine, lcsh:QH426-470, Population, Single-nucleotide polymorphism, Biology, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, Genes, Reporter, Gene expression, Genetics, SNP, Humans, Genetics(clinical), Genetic Predisposition to Disease, Allele, Cloning, Molecular, education, lcsh:RC31-1245, Gene, Genetics (clinical), 030304 developmental biology, Cell Line, Transformed, 0303 health sciences, education.field_of_study, Reporter gene, Intron, Asthma, Introns, respiratory tract diseases, lcsh:Genetics, ADAM Proteins, 030228 respiratory system, Mutagenesis, Site-Directed, Research Article |
| الوصف: | Background ADAM33 has been identified as an asthma-associated gene in an out-bred population. Genetic studies suggested that the functional role of this metalloprotease was in airway remodeling. However, the mechanistic roles of the disease-associated SNPs have yet to be elucidated especially in the context of the pathophysiology of asthma. One disease-associated SNP, BC+1, which resides in intron BC toward the 5' end of ADAM33, is highly associated with the disease. Methods The region surrounding this genetic variant was cloned into a model system to determine if there is a regulatory element within this intron that influences transcription. Results The BC+1 protective allele did not impose any affect on the transcription of the reporter gene. However, the at-risk allele enforced such a repressive affect on the promoter that no protein product from the reporter gene was detected. These results indicated that there exists within intron BC a regulatory element that acts as a repressor for gene expression. Moreover, since SNP BC+1 is a common genetic variant, this region may interact with other undefined regulatory elements within ADAM33 to provide a rheostat effect, which modulates pre-mRNA processing. Thus, SNP BC+1 may have an important role in the modulation of ADAM33 gene expression. Conclusion These data provide for the first time a functional role for a disease-associated SNP in ADAM33 and begin to shed light on the deregulation of this gene in the pathophysiology of asthma. |
| تدمد: | 1471-2350 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c9f5c72f7efdbc44891506a21f6cc1fb https://pubmed.ncbi.nlm.nih.gov/17640346 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....c9f5c72f7efdbc44891506a21f6cc1fb |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14712350 |
|---|