MTP Gene Variants and Response to Lomitapide in Patients with Homozygous Familial Hypercholesterolemia.

MTP Gene Variants and Response to Lomitapide in Patients with Homozygous Familial Hypercholesterolemia. J Atheroscler Thromb. 2016 May 10; Authors: Kolovou GD, Kolovou V, Papadopoulou A, Watts GF 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. PMID: 27170061 [PubMed - as supplied by publisher]
Source: Journal of Atherosclerosis and Thrombosis - Category: Cardiology Tags: J Atheroscler Thromb Source Type: research