Document Detail

Association of Hck genetic polymorphisms with gene expression and COPD.
MedLine Citation:
PMID:  17024369     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-09-26
Journal Detail:
Title:  Human genetics     Volume:  120     ISSN:  0340-6717     ISO Abbreviation:  Hum. Genet.     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2007-01-11     Completed Date:  2007-04-16     Revised Date:  2012-06-05    
Medline Journal Info:
Nlm Unique ID:  7613873     Medline TA:  Hum Genet     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  681-90     Citation Subset:  IM    
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.
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MeSH Terms
DNA Mutational Analysis
Flow Cytometry
Gene Expression*
Gene Frequency
Linkage Disequilibrium
Middle Aged
Mutagenesis, Insertional
Polymorphism, Single Nucleotide*
Proto-Oncogene Proteins c-hck / genetics*,  metabolism
Pulmonary Disease, Chronic Obstructive / genetics*
RNA, Messenger / genetics,  metabolism
Sequence Deletion
Grant Support
5R01HL064068-04/HL/NHLBI NIH HHS
Reg. No./Substance:
0/RNA, Messenger; EC protein, human; EC Proteins c-hck

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