title: MTP Gene Variants and Response to Lomitapide in Patients with Homozygous Familial Hypercholesterolemia.
abstract: 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.
authors.affiliation: Cardiology Department, Onassis Cardiac Surgery Center Athens.
authors.forename: Genovefa D
authors.initials: GD
authors.lastname: Kolovou
authors.forename: Vana
authors.initials: V
authors.lastname: Kolovou
authors.forename: Anna
authors.initials: A
authors.lastname: Papadopoulou
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Watts
mesh_terms: D000328:Adult; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D000924:Anticholesteremic Agents; C473731:BMS201038; D001562:Benzimidazoles; D002352:Carrier Proteins; C106092:microsomal triglyceride transfer protein