F8 haplotype and inhibitor risk: results from the Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort. (7th September 2012)

• Record Type: Journal Article
• Authors: Schwarz, J.; Astermark, J.; Menius, E. D.; Carrington, M.; Donfield, S. M.; Gomperts, E. D.; Nelson, G. W.; Oldenburg, J.; Pavlova, A.; Shapiro, A. D.; Winkler, C. A.; Berntorp, E.
• Is Part Of: Haemophilia. Volume 19:Number 1(2013:Jan.)
• Page Start: 113
• Page End: 118
• Publication Date: 2012-09-07
• Subjects: Hemophilia -- Periodicals; 616.1572005
• DOI: 10.1111/hae.12004
• Languages: English
• ISSNs: 1351-8216

Abstract

<abstract abstract-type="main" id="hae12004-abs-0001"> <title>Summary</title> <p>Ancestral background, specifically African descent, confers higher risk for development of inhibitory antibodies to factor VIII (FVIII) in haemophilia A. It has been suggested that differences in the distribution of FVIII gene (<italic>F8</italic>) haplotypes, and mismatch between endogenous <italic>F8</italic> haplotypes and those comprising products used for treatment could contribute to risk. Data from the Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort were used to determine the association between <italic>F8</italic> haplotype 3 (H3) vs. haplotypes 1 and 2 (H1 + H2) and inhibitor risk among individuals of genetically determined African descent. Other variables known to affect inhibitor risk including type of <italic>F8</italic> mutation and human leucocyte antigen (HLA) were included in the analysis. A second research question regarding risk related to mismatch in endogenous <italic>F8</italic> haplotype and recombinant FVIII products used for treatment was addressed. Haplotype 3 was associated with higher inhibitor risk among those genetically identified (<italic>N</italic> = 49) as of African ancestry, but the association did not remain significant after adjustment for <italic>F8</italic> mutation type and the HLA variables. Among subjects of all racial ancestries enrolled in HIGS who reported early use of recombinant products (<italic>N</italic> = 223), mismatch in endogenous haplotype and the FVIII proteins constituting the products used did not confer greater risk for inhibitor development. Haplotype 3 was not an independent predictor of inhibitor risk. Furthermore, our findings did not support a higher risk of inhibitors in the presence of a haplotype mismatch between the FVIII molecule infused and that of the individual.</p> </abstract>