Heterozygous Korat cats with LDL receptor mutation are asymptomatic and normolipidemic

Human familial hypercholesterolemia (FH) is a genetic disease and the most potent risk factor for atherosclerosis, where both heterozygous and homozygous patients develop severe clinical disease. We have recently described in Korat cats a low-density lipoprotein receptor (LDLR) linked atherosclerosis in homozygous cats with severe alterations in cholesterol levels. Mutations in LDLR are the most common cause of FH in humans. Here we investigate the clinical phenotype of heterozygous Korat cats with a nonsense variant in the LDLR gene. Altogether 76 adult cats with confirmed LDLR genotype information were included. We collected health data from the cat owners, studied the most common human FH-associated plasma biomarkers (total, LDL- and HDL-cholesterol, and triglycerides) and screened for alterations in other established dyslipidemia markers to identify feline patients with a possible risk for CVD events. The health survey revealed no clinical signs indicative of cardiovascular disease or lipid metabolism disorders. We detected a minor increase in plasma total and LDL-cholesterol concentrations in the heterozygous cats, but the magnitude of difference between heterozygous and wild-type cats was not considered clinically relevant. In conclusion, unlike humans, Korat cats with LDLR heterozygosity maintain a normolipidemic state comparable to their wild-type counterparts, are asymptomatic and without a risk for atherosclerosis. Species-specific differences in cholesterol clearance are likely the reason why the condition appears to be recessive in cats with a resistance to atherosclerosis. Heterozygous cats cannot be screened and identified with conventional clinical lipidology markers but require LDLR genotyping.