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Blood, 1 March 2006, Vol. 107, No. 5, pp. 2200-2207. Prepublished online as a Blood First Edition Paper on November 22, 2005; DOI 10.1182/blood-2005-06-2338. This Article Full Text (PDF) Supplemental Tables All Versions of this Article: 2005-06-2338v1 107/5/2200    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Chien, J. W Articles by Clark, J. G Search for Related Content PubMed PubMed Citation Articles by Chien, J. W Articles by Clark, J. G Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 13, 2005 Accepted October 25, 2005 Genetic variation in bactericidal/permeability increasing protein influences the risk of developing rapid airflow decline after hematopoietic cell transplantation Jason W Chien*, Lue Ping Zhao, John A Hansen, Wen Hong Fan, Tanyalak Parimon, and Joan G Clark Clinical Research Division and Public Health Science Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA * Corresponding author; email: jchien{at}fhcrc.org. Innate immunity is involved in the biology of graft versus host disease and common airways diseases. We screened 15 genes in this pathway using a haplotype approach to identify potential candidate genes that may be involved in the development of airflow obstruction after hematopoietic cell transplant. Sixty-nine haplotype tagging single nucleotide polymorphisms were selected for assessment in a discovery cohort (N=363). Significant associations were validated in a validation cohort (N=209). Expression of the candidate gene was demonstrated by detecting gene transcript and protein in malignant and normal small airway epithelial cells. In the discovery cohort, 133 patients developed significant airflow decline. Four patient and donor bactericidal permeability increasing (BPI) haplotypes were associated with a 2 to 3-fold increased risk for developing significant airflow decline (p-values 0.004 to 0.038). This association was confirmed in the validation cohort, which had 66 patients with significant airflow decline, with 9 significant haplotypes (p-values 0.013 to 0.043). BPI gene transcript and protein was detected in airway epithelial cells. These results suggest mutations in the BPI gene significantly influence the risk for developing rapid airflow decline after hematopoietic cell transplantation and may represent a novel therapeutic target for this form of airways disease. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. W. Chien, M. J. Boeckh, J. A. Hansen, and J. G. Clark Lipopolysaccharide binding protein promoter variants influence the risk for Gram-negative bacteremia and mortality after allogeneic hematopoietic cell transplantation Blood, February 15, 2008; 111(4): 2462 - 2469. [Abstract] [Full Text] [PDF] A. Mullally and J. Ritz Beyond HLA: the significance of genomic variation for allogeneic hematopoietic stem cell transplantation Blood, February 15, 2007; 109(4): 1355 - 1362. [Abstract] [Full Text] [PDF]

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