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The loss-of-function mutation of the apolipoprotein (APO) B gene (APOB) in Holstein cattle accounts for increased losses in calves that are homozygous for this mutation. Heterozygous carriers of the APOB mutation are clinically healthy but show decreased concentrations of plasma cholesterol and lipoproteins. So far, the metabolic effects of the mutation have only been investigated in heterozygous calves, bulls, and nonlactating females. In high-yielding dairy cows, a marked decrease in cholesterol concentration in plasma during early lactation is part of the usual metabolic changes. Given the essential role of cholesterol in fatty acid and lipid metabolism, a specific effect of the APOB mutation on metabolism and performance in dairy cows is expected. Therefore, the aim of the present study was to investigate the effects of different APOB genotypes on metabolic parameters, hepatic metabolism, and lactation and …