Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness
| Autor: | Tim Keith, Jason Simon, Brooke Hayward, Alison Walsh, Dana Torrey, Cuss Francis M, Joann Dubois, Rene Gibson, Shelby P. Umland, Michelle Thackston, John W. Holloway, Kristina Allen, Ziying Liu, Paul Van Eerdewegh, Michael Fitzgerald, Joyce McKenny, Yun Feng, S. Rorke, Richard G. Del Mastro, Ron Adair, Hui Huang, Mei Wang, Youssef Benchekroun, Lisa Saracino, Josée Dupuis, Alex Pedan, Sunil Pandit, Melvyn R. Danzig, Susan P. Manning, Stephen T. Holgate, Karen Braunschweiger, Randall D. Little, Joanne B. Clough, Robert W. Egan, Neva J. Capparell, Kathy Falls, Colleen Folz, Alicia Bawa |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Positional cloning
Population ADAM33 Chromosomes Human Pair 20 Locus (genetics) Biology Polymorphism Single Nucleotide Linkage Disequilibrium White People Gene Frequency Genetic linkage medicine Humans Genetic Predisposition to Disease education Asthma education.field_of_study Multidisciplinary Genome Human Haplotype Chromosome Mapping Metalloendopeptidases Exons medicine.disease Introns United Kingdom United States respiratory tract diseases ADAM Proteins Phenotype Haplotypes Bronchial hyperresponsiveness Case-Control Studies Immunology Bronchial Hyperreactivity Lod Score |
| Zdroj: | Nature. 418:426-430 |
| ISSN: | 1476-4687 0028-0836 |
| DOI: | 10.1038/nature00878 |
| Popis: | Asthma is a common respiratory disorder characterized by recurrent episodes of coughing, wheezing and breathlessness. Although environmental factors such as allergen exposure are risk factors in the development of asthma, both twin and family studies point to a strong genetic component1,2. To date, linkage studies have identified more than a dozen genomic regions linked to asthma3. In this study, we performed a genome-wide scan on 460 Caucasian families and identified a locus on chromosome 20p13 that was linked to asthma (log10 of the likelihood ratio (LOD), 2.94) and bronchial hyperresponsiveness (LOD, 3.93). A survey of 135 polymorphisms in 23 genes identified the ADAM33 gene4 as being significantly associated with asthma using case-control, transmission disequilibrium and haplotype analyses (P = 0.04–0.000003). ADAM proteins are membrane-anchored metalloproteases with diverse functions, which include the shedding of cell-surface proteins such as cytokines and cytokine receptors5. The identification and characterization of ADAM33, a putative asthma susceptibility gene identified by positional cloning in an outbred population, should provide insights into the pathogenesis and natural history of this common disease. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|