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Blood, 15 June 2008, Vol. 111, No. 12, pp. 5721-5726. Prepublished online as a Blood First Edition Paper on January 10, 2008; DOI 10.1182/blood-2007-02-074849. This Article Full Text (PDF) Supplemental Table All Versions of this Article: blood-2007-02-074849v1 111/12/5721    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 Ashley-Koch, A. E. Articles by Telen, M. J. Search for Related Content PubMed PubMed Citation Articles by Ashley-Koch, A. E. Articles by Telen, M. J. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 16, 2007 Accepted November 14, 2007 Identification of genetic polymorphisms associated with risk for pulmonary hypertension in sickle cell disease Allison E. Ashley-Koch*, Laine Elliott, Melanie E. Kail, Laura M. De Castro, Jude Jonassaint, Terry L. Jackson, Jennifer Price, Kenneth I Ataga, Marc C Levesque, J Brice Weinberg, Eugene P Orringer, Ann Collins, Jeffery M Vance, and Marilyn J. Telen Department of Medicine, Duke University and VA Medical Centers, Durham, NC Department of Medicine, University of North Carolina, Chapel Hill, NC Miami Institute for Human Genetics, University of Miami, Miami, FL * Corresponding author; email: allison.ashleykoch{at}duke.edu. Up to thirty percent of adult patients with sickle cell disease (SCD) will develop pulmonary hypertension (pHTN), a complication associated with significant morbidity and mortality. To identify genetic factors that contribute to risk for pHTN in SCD, we performed association analysis with 297 SNPs in 49 candidate genes in patients with Hb SS who had been screened for pHTN by echocardiography (n=111). Evidence of association was primarily identified for genes in the TG superfamily, including activin A receptor, type II-like 1 (ACVRL1), bone morphogenetic protein receptor 2 (BMPR2), and bone morphogenetic protein 6 (BMP6). The association of pHTN with ACVRL1 and BMPR2 corroborates the previous association of these genes with primary pHTN. Moreover, genes in the TGF pathway have been independently implicated in risk for several sickle cell complications, suggesting that this gene pathway is important in overall sickle cell pathophysiology. Genetic variation in the beta-1-adrenergic receptor (ADRB1) was also associated with pHTN in our dataset. A multiple regression model, which included age and baseline hemoglobin as covariates, retained SNPs in ACVRL1, BMP6 and ADRB1 as independently contributing to pHTN risk. These findings may offer new promise for identifying patients at risk for pHTN, developing new therapeutic targets and reducing the occurrence of this life-threatening SCD complication. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: SNPing away at sickle cell pathophysiology Martin H. Steinberg Blood 2008 111: 5420-5421. [Full Text] [PDF] This article has been cited by other articles: Risk Factors for Pulmonary Hypertension in Sickle Cell Patients Journal Watch Oncology and Hematology, July 8, 2008; 2008(708): 2 - 2. [Full Text] C. R. Morris Mechanisms of Vasculopathy in Sickle Cell Disease and Thalassemia Hematology, January 1, 2008; 2008(1): 177 - 185. [Abstract] [Full Text] [PDF]

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