Platelet response to a small molecule inhibitor of α2β1 integrin is associated with ITGA2 C807T dimorphism

Abstract

High expression of the collagen receptor, α2β1 integrin, on platelets of ITGA2 807T-allele carriers has been identified as a risk factor for thromboembolic conditions, and α2β1 inhibitors are considered to be potential therapeutic agents. In 59 genotyped individuals, we measured α2 expression levels on platelets and analyzed platelet adhesion to collagen under flow conditions. A sulfonamide-type small-molecule inhibitor of α2β1 integrin decreased average platelet adhesion in individuals with the C/T807T genotype but not in those harboring C807C. Thus, genotype can be used to select a human subpopulation that has the highest probability of showing a positive response to α2β1 inhibitors.

Keywords:

• Collagen receptor
• integrin
• inhibitor
• platelets
• polymorphism

Acknowledgments

The authors thank Karin Laurén and Mira Friman for skillful technical assistance.

Declaration of interest

L.N., J.N., P.O. and A.M. are former employees of BioTie Therapies Corp. J.H. is a former consultant for BioTie Therapies Corp.