| Association of Hck genetic polymorphisms with gene expression and COPD. | |
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MedLine Citation:
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PMID: 17024369 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Polymorphonuclear leukocytes (PMNs) are major effector cells in the chronic airway inflammation in chronic obstructive pulmonary disease (COPD). PMN degranulation is associated with degradation of extracellular matrix and tissue damage. Hck is an essential molecule in the signaling pathway regulating PMN degranulation. We hypothesized that polymorphisms affect the expression level of Hck, which, in turn, modulates PMN mediator release and tissue damage and influences the development of COPD. Here we systematically investigated genetic tag polymorphisms of the Hck gene, Hck mRNA and protein expression pattern in PMNs, and PMN mediator release (myeloperoxidase) in 60 healthy white subjects, and assessed their association with the use of several genetic models. The association of genetic polymorphisms with COPD-related phenotypes was determined in the lung healthy study cohort (LHS). We identified a novel 15 bp insertion/deletion polymorphism (8,656 L/S) in intron 1 of the Hck gene, which was associated with differential expression of Hck protein and PMN myeloperoxidase release. In the LHS cohort, there was significant interaction between the 8,656 L/S polymorphism and smoking on baseline lung function and 8,656 L/S was associated with bronchodilator response. These data suggest that the insertion/deletion polymorphism could be a functional polymorphism of the Hck gene, may contribute to COPD pathogenesis and modify COPD-related phenotypes. |
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Authors:
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Xiaozhu Zhang; Salahaddin Mahmudi-Azer; John E Connett; Nicholas R Anthonisen; Jian-Qing He; Peter D Paré; Andrew J Sandford |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2006-09-26 |
Journal Detail:
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Title: Human genetics Volume: 120 ISSN: 0340-6717 ISO Abbreviation: Hum. Genet. Publication Date: 2007 Jan |
Date Detail:
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Created Date: 2007-01-11 Completed Date: 2007-04-16 Revised Date: 2012-06-05 |
Medline Journal Info:
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Nlm Unique ID: 7613873 Medline TA: Hum Genet Country: Germany |
Other Details:
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Languages: eng Pagination: 681-90 Citation Subset: IM |
Affiliation:
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James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research , St. Paul's Hospital, University of British Columbia, 1081 Burrard Street, Room 166, Vancouver, BC, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult DNA Mutational Analysis Female Flow Cytometry Gene Expression* Gene Frequency Genotype Humans Immunohistochemistry Linkage Disequilibrium Male Middle Aged Mutagenesis, Insertional Mutation Polymorphism, Single Nucleotide* Proto-Oncogene Proteins c-hck / genetics*, metabolism Pulmonary Disease, Chronic Obstructive / genetics* RNA, Messenger / genetics, metabolism Sequence Deletion |
| Grant Support | |
ID/Acronym/Agency:
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5R01HL064068-04/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/RNA, Messenger; EC 2.7.10.2/HCK protein, human; EC 2.7.10.2/Proto-Oncogene Proteins c-hck |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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