Department of Toxicology, Oncology and Molecular Pathology Unit, University of Cagliari, Italy.
Nutr Metab Cardiovasc Dis. 2013 Aug;23(8):732-6. doi: 10.1016/j.numecd.2012.05.009. Epub 2012 Jul 12.
The complete absence of the lysosomal acid lipase (LAL) enzyme function causes Wolman's Disease that is fatal within the first six months of life. Subtotal defects cause Cholesteryl ester storage disease (CESD), an autosomal recessive disorder leading to hepatic steatosis, fibrosis, micronodular cirrhosis, combined hyperlipidemia with low HDL-cholesterol, increased risk for atherosclerosis, premature death. Since the frequency of the Exon 8 splice junction mutation (c.894 G > A, E8SJM), the CESD leading mutation, is not rare in the general population (allele frequency 0.0025), we investigated the impact of this mutation on serum lipid profile in E8SJM carriers.
We collected E8SJM carriers both form genetic study-population analysis and from Outpatient Lipid Clinics and then we assessed their serum lipid profile. We found thirteen individuals heterozygote for E8SJM. Most of them were Germans, three Spanish and two Italian. We found a significant increase in total cholesterol levels in both sexes with E8SJM mutation, leading to a significant increase in LDL cholesterol in males.
Our results show that LAL E8SJM carriers have an alteration in lipid profile with a Polygenic Hypercholesterolemia phenotype, leading to an increase in cardiovascular risk profile.
溶酶体酸性脂肪酶（LAL）完全缺乏会导致沃曼氏病（Wolman's Disease），患儿在出生后的头六个月内死亡。不完全缺陷会导致胆固醇酯贮积症（Cholesteryl ester storage disease，CESD），这是一种常染色体隐性遗传病，导致肝脂肪变性、纤维化、小结节性肝硬化、混合性高脂血症伴低 HDL-胆固醇、动脉粥样硬化风险增加和早逝。由于exon 8 剪接连接突变（c.894 G > A，E8SJM），即 CESD 的主要突变，在普通人群中的频率并不罕见（等位基因频率为 0.0025），因此我们研究了这种突变对 E8SJM 携带者血清脂质谱的影响。
我们从遗传研究人群分析和门诊脂质诊所收集了 E8SJM 携带者，然后评估了他们的血清脂质谱。我们发现了 13 名 E8SJM 杂合子个体。他们大多是德国人，有 3 名西班牙人和 2 名意大利人。我们发现 E8SJM 突变的男性和女性总胆固醇水平均显著升高，导致 LDL 胆固醇显著升高。
我们的结果表明，LAL E8SJM 携带者的脂质谱发生了改变，表现为多基因高胆固醇血症表型，增加了心血管风险。
