Polymorphisms within the APOBR gene are highly associated with milk levels of prognostic ketosis biomarkers in dairy cows

Essentially all high-yielding dairy cows experience a negative energy balance during early lactation leading to increased lipomobilization, which is a normal physiological response. However, a severe energy deficit may lead to high levels of ketone bodies and, subsequently, to subclinical or clinical ketosis. It has previously been reported that the ratio of glycerophosphocholine to phosphocholine in milk is a prognostic biomarker for the risk of ketosis in dairy cattle. It was hypothesized that this ratio reflects the ability to break down blood phosphatidylcholine as a fatty acid resource. In the current study, 248 animals from a previous study were genotyped with Illumina BovineSNP50 BeadChip, and genome-wide association studies were carried out for the milk levels of phosphocholine, glycerophosphocholine, and the ratio of both metabolites. It was demonstrated that the latter two traits are heritable with h2 = 0.43 and h2 = 0.34, respectively. A major quantitative trait locus was identified on cattle chromosome 25. The APOBR gene, coding for the apolipoprotein B receptor, is located within this region and was analyzed as a candidate gene. The analysis revealed highly significant associations of polymorphisms within the gene with glycerophosphocholine as well as the metabolite ratio. These findings support the hypothesis that differences in the ability to take up blood phosphatidylcholine from low-density lipoproteins play an important role in early lactation metabolic stability of dairy cows and indicate APOBR to contain a causative variant.