Muntoni Sandro, Pisciotta Livia, Muntoni Sergio, Bertolini Stefano
Oncology and Molecular Pathology Unit, Department of Biomedical Sciences, University of Cagliari, Italy; Centre for Metabolic Diseases and Atherosclerosis, The ME.DI.CO. Association, Cagliari, Italy.
Department of Internal Medicine, University of Genova, Italy.
J Clin Lipidol. 2015 Jan-Feb;9(1):103-6. doi: 10.1016/j.jacl.2014.08.009. Epub 2014 Aug 30.
Previous studies have shown that patients with autosomal recessive hypercholesterolemia (ARH) resulting from mutations in LDLRAP1 gene have a less severe cardiovascular involvement than familial hypercholesterolemia homozygotes, lower levels of low-density lipoprotein cholesterol (LDL-C), and higher levels of high-density lipoprotein cholesterol (HDL-C). In addition, ARH patients seem to be more responsive to the lipid-lowering drugs. The aim was to test the effect of a combined drug treatment in an ARH patient in the absence of plasmapheresis.
Here we report the lipid-lowering effect of rosuvastatin (60 mg/day) associated with ezetimibe (10 mg/day) in a single ARH patient. The sequencing of LDLRAP1 gene showed that the patient was homozygous for the c.432insA mutation. During a 6-month treatment, we observed an 80% reduction of LDL-C and a significant increase of HDL-C and ApoA-I. Some sequence variations in PCSK9 and NPC1L1 genes found in this patient may have contributed to the success of drug treatment.
Our findings, although limited to a single case, suggest that in many ARH patients the LDL-C goal may be reached with the more potent statins associated with ezetimibe in the absence of extracorporeal procedures.
既往研究表明，因低密度脂蛋白受体衔接蛋白1（LDLRAP1）基因突变导致的常染色体隐性高胆固醇血症（ARH）患者，其心血管受累程度较家族性高胆固醇血症纯合子轻，低密度脂蛋白胆固醇（LDL-C）水平较低，高密度脂蛋白胆固醇（HDL-C）水平较高。此外，ARH患者似乎对降脂药物反应更敏感。本研究旨在测试在无血浆置换情况下联合药物治疗对一名ARH患者的疗效。
在此，我们报告了瑞舒伐他汀（60毫克/天）联合依折麦布（10毫克/天）对一名ARH患者的降脂效果。LDLRAP1基因测序显示，该患者为c.432insA突变纯合子。在为期6个月的治疗期间，我们观察到LDL-C降低了80%，HDL-C和载脂蛋白A-I（ApoA-I）显著升高。该患者中发现的前蛋白转化酶枯草溶菌素9（PCSK9）和尼曼匹克C1样蛋白1（NPC1L1）基因的一些序列变异可能有助于药物治疗取得成功。
我们的研究结果虽然仅限于单个病例，但表明在许多ARH患者中，在无体外治疗的情况下，联合使用更有效的他汀类药物和依折麦布可能达到LDL-C治疗目标。
