Compound heterozygosity at the sphingomyelin phosphodiesterase-1 (SMPD1) gene is associated with low HDL cholesterol
Compound heterozygosity at the sphingomyelin phosphodiesterase-1 (SMPD1) gene is associated with low HDL cholesterol
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DOI：
10.1007/s00439-002-0893-1
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发表时间：
2003-05-01
期刊：
影响因子：
5.3
通讯作者：
Marcil, M
中科院分区：
文献类型：
--
作者：
Lee, CY;Krimbou, L;Marcil, M
A型和B型Niemann-Pick病(NPD)是由于酸性鞘磷脂酶(ASMase)活性不足而导致的脂肪储存障碍，从而导致神经鞘磷脂在组织中积累。在这项研究中，我们调查了两名被诊断为B型NPD的家庭成员，他们的血浆高密度脂蛋白胆固醇(HDL-C)严重下降。先证者为48岁男性，高密度脂蛋白胆固醇为0.30 mmol/L(12 mg/dl)，其姐姐高密度脂蛋白胆固醇为0.45 mm ol/L(17 mg/dl)，患有严重的早发冠状动脉疾病。两例患者均有高甘油三酯血症。皮肤成纤维细胞中测得的aSMase活性明显降低。编码aSMase的SMPD1基因在受影响的受试者和所有家庭成员中被测序。在这两个患者中都发现了复合杂合子(AR608和R441X)。携带AR608突变的携带者往往有中度到重度的低密度脂蛋白水平，而携带R441X突变的携带者，尽管只存在于年轻受试者中(
Type A and B forms of Niemann-Pick disease (NPD) are lipid storage disorders caused by deficient activity of the enzyme acid sphingomyelinase (aSMase) and the resulting accumulation of sphingomyelin in tissues. In the present study, we investigated two family members who had been diagnosed with Type B NPD and who had a severe decrease in plasma high density lipoprotein cholesterol (HDL-C). The proband (a 48-year-old male) had an HDL-C of 0.30 mmol/l (12 mg/dl) and his sister had values of 0.45 mmol/l (17 mg/dl) with severe premature coronary artery disease (CAD). Hypertriglyceridemia was found in both cases. aSMase activity measured in skin fibroblasts appeared markedly depressed. The SMPD1 gene, coding for aSMase, was sequenced in affected subjects and all family members. Compound heterozygosity (AR608 and R441X) was identified in both affected patients. Carriers of the AR608 mutation tended to have moderately to severe decreased HDL-C levels, whereas carriers of the R441X mutation, although present only in young subjects (