TY - JOUR
T1 - MTP gene variants and response to lomitapide in patients with homozygous familial hypercholesterolemia
AU - Kolovou, G.D.
AU - Kolovou, V.
AU - Papadopoulou, A.
AU - Watts, Gerald
PY - 2016
Y1 - 2016
N2 - © 2016, Japan Atherosclerosis Society. All rights reserved.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
AB - © 2016, Japan Atherosclerosis Society. All rights reserved.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
U2 - 10.5551/jat.34777
DO - 10.5551/jat.34777
M3 - Article
C2 - 27170061
SN - 1340-3478
VL - 23
SP - 878
EP - 883
JO - Journal of Atherosclerosis and Thrombosis
JF - Journal of Atherosclerosis and Thrombosis
IS - 7
ER -