Journal
HAEMOPHILIA
Volume 19, Issue 1, Pages 113-118Publisher
WILEY
DOI: 10.1111/hae.12004
Keywords
F8 haplotype; FVIII inhibitors; haplotype mismatch
Categories
Funding
- Baxter BioScience
- Frederick National Laboratory for Cancer Research, National Institutes of Health (NIH) [HHSN261200800001E]
- Wyeth
- Research Fund at Malmo University Hospital
- NIH, National Institute of Child Health and Human Development [R01-HD-41224]
- Bayer
- Inspiration Biopharmaceuticals, Inc.
- Grifols, Inc.
- Baxter
- Biogen Idec
- Biotest
- CSL Behring
- Grifols
- Inspiration Biopharmaceuticals
- NovoNordisk
- Octapharma
- Swedish Orphan Biovitrum
- Wyeth/Pfizer
- NATIONAL CANCER INSTITUTE [ZIABC010022, ZIABC010791] Funding Source: NIH RePORTER
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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 (F8) haplotypes, and mismatch between endogenous F8 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 F8 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 F8 mutation and human leucocyte antigen (HLA) were included in the analysis. A second research question regarding risk related to mismatch in endogenous F8 haplotype and recombinant FVIII products used for treatment was addressed. Haplotype 3 was associated with higher inhibitor risk among those genetically identified (N = 49) as of African ancestry, but the association did not remain significant after adjustment for F8 mutation type and the HLA variables. Among subjects of all racial ancestries enrolled in HIGS who reported early use of recombinant products (N = 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.
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