Evaluation of variants in the ENTPD1 (g.209A>G, g.291A>T e g.338G>A) and ENTPD2 (g.464G>A) genes in athletic horses with exercise-induced pulmonary haemorrhage

Abstract

Abstract Background Exercise-induced pulmonary haemorrhage (EIPH) is characterized by the presence of blood from the lungs in the tracheobronchial tree after intense exercise in athletic horses. Despite the high prevalence of EIPH in horses, the primary aetiology remains unknown. Mutations in genes encoding CD39 and CD39L1 (ENTPD1 and ENTPD2, respectively) were previously reported as potential genetic causes involved in EIPH pathogenesis. However, the role these mutations associated with haemostatic functions is unknown. Results To investigate the association between EIPH and mutations (g.290A > G, g.291A > T, and g.338G > A) in the ENTPD1 and (g.646G > A) ENTPD2 genes, 76 Thoroughbred horses diagnosed with EIPH and 56 without clinical signs of EIPH (control group) by trachea-bronchial endoscopy were genotyped. The g.290A > G and g.338G > A mutations were linked, explaining why the same results were found in all horses. Both of these mutations were observed in 56.6% of homozygous and 39.5% of heterozygous EIPH horses. In the control group, 66.1% and 28.6% of horses were homozygous and heterozygous for these mutations, respectively. Approximately 2.6% (2/76) of EIPH horses and no control horses (0/56) were homozygous for the g.291A > T mutation. Meanwhile, in the EIPH group, there were 1.5% (1/68) homozygotes and 23.5% (16/58) heterozygotes for the g.464G > A mutation. In the control group, this mutation was observed only in heterozygotes (15.6%, 7/45). There was no significant difference between groups for any of the mutations. Conclusions The mutations previously described in the genes encoding CD39 and CD39L1 enzymes are highly present in the studied population. A possible breed predisposition may be involved; however, no association was found between the occurrence of EIPH and the presence of these mutations in the ENTPD1 and ENTPD2 genes in Thoroughbred horses in this study.