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

作者：Kolovou, Genovefa D.^*; Kolovou, Vana; Papadopoulou, Anna; Watts, Gerald F.

来源：Journal of Atherosclerosis and Thrombosis, 2016, 23(7): 878-883.

DOI：10.5551/jat.34777

• Homozygous familial hypercholesterolemia
• Microsomal transfer protein
• Lomitapide
• MTP gene

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.

• 出版日期2016