MTP gene variants and response to lomitapide in patients with homozygous familial hypercholesterolemia

Homozygous familial hypercholesterolemia (hofh) is a rare genetic disorder,which leads to premature cardiovascular diseases. microsomal triglyceride transport protein (mtp) inhibitors,such as lomitapide,offer a new therapeutic approach for treating these patients. we evaluated the lipid lowering (ll) efficacy of lomitapide according to several gene variants in mtp. four clinically and/ or molecularly defined hofh patients were treated with lomitapide in addition to conventional high intensity ll therapy and regular lipoprotein apheresis. two patients responded to the therapy,with a significant reduction of ldl cholesterol (ldl-c>50%,hyper-responders). sequencing of all exonic and intronic flanking regions of the mtp gene in all patients revealed 36 different variants. the hyper-responders to lomitapide shared six common variants: rs17533489,rs79194015,rs745075,rs41275715,rs1491246,and rs17533517,which were not seen in hypo-responders (reduction in ldl-c<50%). we suggest that in hofh variants in the mtp gene may impact on the therapeutic response to lomitapide,but this requires further investigation. © 2016,japan atherosclerosis society. all rights reserved.