SEARCH:   Advanced

Blood, 15 March 2004, Vol. 103, No. 6, pp. 2391-2396. Prepublished online as a Blood First Edition Paper on November 13, 2003; DOI 10.1182/blood-2003-09-3015. This Article Full Text (PDF) All Versions of this Article: 2003-09-3015v1 103/6/2391    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 Hoppe, C. Articles by Styles, L. Search for Related Content PubMed PubMed Citation Articles by Hoppe, C. Articles by Styles, L. Social Bookmarking                   What's this? Submitted September 3, 2003 Accepted October 31, 2003 Gene interactions and stroke risk in children with sickle cell anemia Carolyn Hoppe*, William Klitz, Suzanne Cheng, Ray Apple, Lori Steiner, Lara Robles, Tom Girard, Elliott Vichinsky, and Lori Styles Department of Hematology/Oncology, Children's Hospital & Research Center at Oakland, Oakland, CA, USA Department of Human Genetics, Roche Molecular Systems Inc., Alameda, CA, USA * Corresponding author; email: choppe{at}mail.cho.org. Stroke is a devastating complication of sickle cell anemia (SCA), affecting up to 30% children. Despite the relative frequency of stroke in SCA, few predictors of risk exist. Because stroke in SCA is likely a multifactorial disease, analysis of the combined effect of multiple genetic variants may prove more successful than evaluation of individual candidate genes. We genotyped 230 children with SCA for 104 polymorphisms among 65 candidate vascular genes to identify risk associations with stroke. Patients were phenotyped based on magnetic resonance imaging/angiography (MRI/MRA) findings into large (LV) vs. small vessel (SV) disease stroke subgroups. Specific polymorphisms in the IL4R 503, TNF (-308), and ADRB2 27 genes were independently associated with stroke susceptibility in the LV stroke subgroup, while variants in the VCAM1 (-1594) and LDLR NcoI genes were associated with SV stroke risk. The combination of TNF (-308)GG homozygosity and the IL4R 503P variant carrier status was associated with a particularly strong predisposition to LV stroke (OR = 5.5, 95% CI = 2.3-13.1). We show that several candidate genes may play a role in predisposition to specific stroke subtypes in children with SCA. If confirmed, these results provide a basis for population screening and targeted intervention to prevent stroke in SCA. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. S. Roach, M. R. Golomb, R. Adams, J. Biller, S. Daniels, G. deVeber, D. Ferriero, B. V. Jones, F. J. Kirkham, R. M. Scott, et al. Management of Stroke in Infants and Children: A Scientific Statement From a Special Writing Group of the American Heart Association Stroke Council and the Council on Cardiovascular Disease in the Young Stroke, September 1, 2008; 39(9): 2644 - 2691. [Abstract] [Full Text] [PDF] C. Lee and M. Kong An Interactive Association of Common Sequence Variants in the Neuropeptide Y Gene With Susceptibility to Ischemic Stroke Stroke, October 1, 2007; 38(10): 2663 - 2669. [Abstract] [Full Text] [PDF] C. Hoppe, W. Klitz, K. D'Harlingue, S. Cheng, M. Grow, L. Steiner, J. Noble, R. Adams, L. Styles, and for the Stroke Prevention Trial in Sickle Cell Ane Confirmation of an Association Between the TNF( 308) Promoter Polymorphism and Stroke Risk in Children With Sickle Cell Anemia Stroke, August 1, 2007; 38(8): 2241 - 2246. [Abstract] [Full Text] [PDF] D. M. Iovannisci, E. J. Lammer, L. Steiner, S. Cheng, L. T. Mahoney, P. H. Davis, R. M. Lauer, and T. L. Burns Association Between A Leukotriene C4 Synthase Gene Promoter Polymorphism and Coronary Artery Calcium in Young Women: The Muscatine Study Arterioscler Thromb Vasc Biol, February 1, 2007; 27(2): 394 - 399. [Abstract] [Full Text] [PDF] C. J. Wu, L. Krishnamurti, J. L. Kutok, M. Biernacki, S. Rogers, W. Zhang, J. H. Antin, and J. Ritz Evidence for ineffective erythropoiesis in severe sickle cell disease Blood, November 15, 2005; 106(10): 3639 - 3645. [Abstract] [Full Text] [PDF] Q. Lan, L. Zhang, M. Shen, M. T. Smith, G. Li, R. Vermeulen, S. M. Rappaport, M. S. Forrest, R. B. Hayes, M. Linet, et al. Polymorphisms in Cytokine and Cellular Adhesion Molecule Genes and Susceptibility to Hematotoxicity among Workers Exposed to Benzene Cancer Res., October 15, 2005; 65(20): 9574 - 9581. [Abstract] [Full Text] [PDF] X. Guo, S. Cheng, K. D. Taylor, J. Cui, R. Hughes, M. J. Quinones, I. Bulnes-Enriquez, R. De La Rosa, G. Aurea, H. Yang, et al. Hypertension Genes Are Genetic Markers for Insulin Sensitivity and Resistance Hypertension, April 1, 2005; 45(4): 799 - 803. [Abstract] [Full Text] [PDF] D. M. Ferriero Neonatal Brain Injury N. Engl. J. Med., November 4, 2004; 351(19): 1985 - 1995. [Full Text] [PDF] G. R. Buchanan, M. R. DeBaun, C. T. Quinn, and M. H. Steinberg Sickle Cell Disease Hematology, January 1, 2004; 2004(1): 35 - 47. [Abstract] [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020