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Blood, 1 December 2006, Vol. 108, No. 12, pp. 3739-3745. Prepublished online as a Blood First Edition Paper on August 22, 2006; DOI 10.1182/blood-2006-05-024711. This Article Full Text Full Text (PDF) Supplemental Appendix All Versions of this Article: blood-2006-05-024711v1 108/12/3739    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Astermark, J. Articles by Lefvert, A.-K. Search for Related Content PubMed PubMed Citation Articles by Astermark, J. Articles by Lefvert, A.-K. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Polymorphisms in the TNFA gene and the risk of inhibitor development in patients with hemophilia A Jan Astermark, Johannes Oldenburg, Joyce Carlson, Anna Pavlova, Kaan Kavakli, Erik Berntorp, Ann-Kari Lefvert, and the MIBS Study Group From the Department for Coagulation Disorders and Clinical Chemistry, Malmö University Hospital, Malmö, Sweden; Institute of Transfusion Medicine and Immunohaematology, University Clinic, Frankfurt, Germany; Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Germany; Department of Pediatric Hematology, Ege University Hospital, Izmir, Turkey; and Immunological Research Laboratory, Center for Molecular Medicine and Department of Medicine, Karolinska Institute, Stockholm, Sweden. The HLA class I/II alleles and the tumor necrosis factor (TNFA) locus are closely linked in the MHC complex. We have characterized the causative factor VIII mutation, HLA alleles as well as 4 polymorphisms (–827C>T, –308G>A, –238A>G, and 670A>G) in the TNFA gene in 164 patients (124 severe, 26 moderate, and 14 mild) in 78 families with hemophilia A enrolled in the Malmö International Brother Study (MIBS). Inhibitors were identified in 77.8% of patients with a single haplotype (Hap 2) and 72.7% of the patients with the TNFA –308 A/A genotype within this haplotype compared with 39.7% for TNFA –308 G/G patients and 46.9% for TNFA –308 G/A heterozygotes (OR 4.0; 95% CI, 1.4-11.5; P = .008). The association between the –308 A/A genotype and inhibitors was enhanced in subgroups of patients with severe hemophilia (OR 19.2; 95% CI 2.4-156.5; P < .001) and with inversions (n = 75; OR, 11.8; 95% CI, 1.3-105.1; P = .013). Associations were found for the HLA A26 and B44 alleles, but these were not consistent in the subgroup analysis. Our data imply that the TNFA –308G>A polymorphism within Hap 2 is a useful marker and potential modulator of the immune response to replacement therapy in patients with hemophilia. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Lacroix-Desmazes, A.-M. Navarrete, S. Andre, J. Bayry, S. V. Kaveri, and S. Dasgupta Dynamics of factor VIII interactions determine its immunologic fate in hemophilia A Blood, July 15, 2008; 112(2): 240 - 249. [Abstract] [Full Text] [PDF]

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