Tom E. Howard, MD, PhD, on Bringing Together Knowledge of Genetic Diversity and HLA Molecules for Gene Editing Strategies


The clinical professor in the Department of Human Genetics at University of Texas Rio Grande Valley discussed research on racial differences in the Factor VIII gene that can impact treatment efficacy for hemophilia A.

“Despite having 5 to 7 times as many samples from white individuals and black individuals, we found that that two-thirds of the differences in the FVIII gene were just in the African-American group. We found that striking because up until that time people thought that the FVIII gene was the same in all racial groups, unless you had hemophilia, and then then there was this huge heterogeneity in mutations that cause hemophilia... What we found initially that got us so excited about getting into this field was that within just 11 black individuals [who did not have hemophilia], we found that those 11 individuals express 5 different forms of the FVIII protein.”

Patients with hemophilia A lack the ability to produce normal Factor VIII (FVIII) protein, which is important in blood clotting. As such, one of the main currently available treatment options for hemophilia A is exogenous FVIII proteins. Although exogenous FVIII can help prevent hemophilia bleeds in many patients, some patients develop an immune response to the exogeneous proteins in the form of FVIII inhibitors. These FVIII inhibitors can prevent them from continuing to benefit from the treatment.

As part of a larger research endeavor, Tom E. Howard, MD, PhD, a clinical professor in the Department of Human Genetics at University of Texas Rio Grande, and his colleagues have noted that patients of certain racial groups are more likely to develop FVIII inhibitors than white patients, and that among healthy people, individuals of African-American descent have greater genetic diversity in the gene that codes for FVIII than do individuals of European ancestry. Research coauthored by Howard that showed evidence for race as a factor that influences FVIII inhibitor development was presented at the the 2023 American Society of Hematology (ASH) Annual Meeting & Exposition, held December 9-12, in San Diego, California.1,2

CGTLive™ sat down with Howard at the conference to discuss this research and its implications. Howard went over the history of research on race and FVIII inhibitor development, as well as the importance of human leukocyte antigen molecules in this area of medicine. He concluded by emphasizing that bringing all of this knowledge together is important for the development of a novel gene editing approach to treating hemophilia that he and his colleagues are currently working on.

1. Bouls R, AlmeidaMA, DiegoVP, et al. Gene-centric association scans of pleiotropic immune-mediated disease genes in the PATH study identify novel determinants of Factor VIII inhibitor risk in hemophilia-A patients and confirm race as an independent predictor. Presented at: ASH 2023 Annual Meeting & Exposition. December 9-12; San Diego, CA. Abstract #1246
2. Ibarra P, Almeida MA, Diego VP, et al. Results from an association-scan of the extended MHC-Class-II region using novel association-based statistical methods establish that DQ allotypes and race independently influence the risk of factor VIII inhibitor development in hemophilia-A patients. Presented at: ASH 2023 Annual Meeting & Exposition. December 9-12; San Diego, CA. Abstract #1247
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