Evaluation of the genes encoding CD39/NTPDase‐1 and CD39L1/NTPDase‐2 in horses with and without abnormal hemorrhage and in horses with pathologic evidence of exercise‐induced pulmonary hemorrhage

Background Exercise-induced pulmonary hemorrhage (EIPH) is a common disorder of equine athletes. The role of polymorphisms in genes encoding hemostasis-regulatory proteins in horses with abnormal hemorrhage is unknown. Objectives The goal of this study was to evaluate the genes encoding 2 ectonucleotidases, CD39/NTPDase-1 and CD39L1/NTPDase-2, and one ecto-5′ nucleotidase, CD73, in horses with abnormal hemorrhage or pathologic changes consistent with EIPH. Methods Twenty-three horses with histories of abnormal hemorrhage, 8 horses with gastrointestinal signs, and 45 healthy horses were evaluated using polymerase chain reaction-based techniques. Formalin-fixed tissues from 21 horses with pathologic changes consistent with EIPH were also evaluated. Results Three single nucleotide polymorphisms (SNPs) were identified in the gene encoding CD39 and one SNP was identified in the gene encoding CD39L1. No SNPs were identified in the gene encoding CD73. CD39 SNPs were identified in 19 of 20 (95%) horses with unexplained hemorrhage and 20 of 21 (95%) horses with pathologic features consistent with EIPH. CD39L1 SNPs were identified in 6 of 20 (30%) horses with unexplained hemorrhage and 8 of 21 (38%) horses with pathologic features consistent with EIPH. CD39 and CD39L1 SNPs were identified in 5 of 8 (62.5%) and one of 8 (12.5%) horses, respectively, presenting with colic or weight loss. CD39 and CD39L1 SNPs were identified in 28 of 45 (62%) and 13 of 45 (28.8%) healthy horses, respectively. Conclusions CD39 and CD39L1 are critically important in maintaining normal hemostasis and limiting inflammation. Further studies are needed to evaluate their role in the pathogenesis of equine EIPH.