Genotyping a SNP in the Endothelial PAS Domain-Containing Protein 1 (EPAS1) Gene: Is It Associated with Mean Pulmonary Arterial Pressures in Yearling Angus Cattle?

At altitudes >1,800 m, measurements of mean pulmonary arterial pressures (mPAP) have been used as an indicator trait of pulmonary hypertension and risk of right-sided heart failure in cattle. Genotypes from a G/A SNP (rs208684340) in the oxygen dependent domain of the endothelial PAS domain protein 1 (EPAS1) gene were determined for yearling Angus cattle classified into mPAP risk categories (low, moderate, high) of heart failure. The A allele of this SNP was hypothesized to be associated with high altitude-induced hypoxemia. The initial objective of this study was to survey genotypic frequencies in Angus cattle at high altitude ranches in the Rocky Mountain west (elevation 1,850 to 2,800 m) and at low altitude ranches (elevation 91 to 1,192 m) in several states. For the latter, a random sampling (n = 118) of 1,275 Angus cattle from low altitude beef production systems in California, Missouri, Iowa, Texas and New Mexico were genotyped. The mPAP phenotype was not collected for cattle residing at these altitudes. The percentage of cattle with genotypes G/G, G/A, and A/A were 64.4, 33.9, and 1.7%, respectively, with a MAF of 18.6%. Also, bulls, steers, and heifers (n = 690 progeny of 99 sires) from 4 Angus seedstock herds managed at high elevation were genotyped. The percentage of these cattle with genotypes G/G, G/A, and A/A were 48.7, 34.3, and 17.0%, respectively. The overall minor allele frequency (MAF; A allele) was 34.1% and mPAP averaged 40.6 ± 8.8 mmHg with a range of 28 to 126 mmHg. The MAF for the low, moderate, and high-risk categories were 35.4, 31.0, and 36.3%, respectively. No differences were observed for MAF between mPAP risk categories (P > 0.05). A second objective of this research was to evaluate the genotype to phenotype association of this SNP with mPAP phenotypes in the Colorado State University Beef Improvement Center (CSU-BIC; elevation 2,150 m) Angus herd. Genotypes from 496 Angus cattle were utilized in the association between this SNP and mPAP. Hardy-Weinberg equilibrium (P = 0.07) was not violated. A linear mixed model analysis with fixed effects of genotype, mPAP date, age and a random effect of sire suggested genotype was not a predictor (P = 0.5) of mPAP and explained only 0.02% of the variation in mPAP. These results do not support the hypothesis that the A allele of this SNP (rs208684340) in EPAS1 gene was associated with altitude-induced hypoxemia in cattle.