Evaluation of EPAS1 variants for association with bovine congestive heart failure [version 1; peer review: 2 approved]

Authors

Michael P. Heaton, U.S. Meat Animal Research CenterFollow
Adam S. Bassett, University of Nebraska-LincolnFollow
Katherine J. Whitman, University of Nebraska-LincolnFollow
Greta M. Krafsur, University of Colorado Denver
Sang M. Lee, University of Nebraska at LincolnFollow
Jaden M. Carlson, University of Nebraska-Lincoln
Halden J. Clark, University of Nebraska-Lincoln
Helen R. Smith, U.S. Meat Animal Research Center
Madeline C. Pelster, University of Nebraska-Lincoln
Veronica Basnayake, Neogen GeneSeek Operations,
Dale M. Grotelueschen, University of Nebraska-LincolnFollow
B. Vander Ley, University of Nebraska-LincolnFollow

ORCID IDs

https://orcid.org/0000-0003-1386-1208

https://orcid.org/0000-0003-0732-2590

Date of this Version

9-5-2019

Citation

2019 Berry D.

Comments

Heaton MP, Bassett AS, Whitman KJ et al. Evaluation of EPAS1 variants for association with bovine congestive heart failure [version 1; peer review: 2 approved] F1000Research 2019, 8:1189 (https://doi.org/10.12688/f1000research.19951.1)

Abstract

Background: Bovine congestive heart failure (BCHF) has become increasingly prevalent in feedlot cattle in the Western Great Plains of North America. BCHF is an untreatable complex condition involving pulmonary hypertension that culminates in right ventricular failure and death. A protein variant of hypoxia-inducible factor 2 alpha (HIF2α, encoded by the endothelial PAS domain-containing protein 1 gene, EPAS1) was previously reported to be associated with pulmonary hypertension at altitudes exceeding 2,000 m. Our aim was to evaluate EPAS1 haplotypes for association with BCHF in feedlot cattle raised at moderate altitudes (1,200 m).

Methods: Paired samples of clinical cases and unaffected controls were collected at four feedlots in Nebraska and Wyoming. Each pair (n =102) was matched for source, pen, breed type, sex, arrival date, and management conditions. Cases were identified by animal caretakers, euthanized, and diagnosis was confirmed at necropsy. Cases were derived from 30 different ranch operations, with the largest source contributing 32. Animals were tested for eight EPAS1 haplotypes encoding 36 possible different diploid combinations.

Results: The common, ancestral EPAS1 haplotype encoding HIF2α with alanine (A) at position 606 and glycine (G) at position 610 was equally frequent in cases and controls (0.67). The EPAS1 variant haplotype reported to be associated with disease (encoding threonine (T) at position 606 and serine (S) at position 610) was not enriched in cases compared with controls (0.21 and 0.25, respectively). Frequencies of other EPAS1 haplotypes (e.g., encoding Q270, L362, or G671) were each less than 0.05 overall. McNemar’s test with 45 discordant pairs showed the linked T606/S610 variant was not associated with BCHF (OR = 0.73, CI 0.38 -1.4, p-value = 0.37).

Conclusions: HIF2α polypeptide variants were not significantly associated with BCHF in feedlot cattle at moderate altitudes. Thus, a wider search is needed to identify genetic risk factors underlying this disease.