School of Basic Medical Sciences, Peking University, Beijing, China.
Am J Med Genet A. 2012 Nov;158A(11):2775-80. doi: 10.1002/ajmg.a.35395. Epub 2012 Sep 28.
Niemann-Pick disease, type C1 (NPC1) is a lipid storage disorder that results in progressive neurological impairment. The NPC1 phenotype is extremely variable and at the individual level is likely influenced by other genetic traits. In addition to residual function of NPC1 protein, we hypothesize that modifier genes, as frequently observed with other autosomal recessive diseases, influence the NPC phenotype. The NPC1 phenotype includes progressive dementia, and the NPC pathology has some overlap with the pathology of Alzheimer disease (AD). Thus, we examined apolipoprotein E (ApoE) and microtubule-associated protein tau (MAPT) polymorphisms in a cohort of 15 NPC1 patients with well characterized longitudinal disease progression. Although we did not find any correlations between disease severity and tau polymorphisms, we found significant associations between ApoE polymorphisms and phenotypic severity. Specifically, ApoE4 and ApoE2 alleles were associated, respectively, with increased and decreased disease severity in this cohort of NPC1 patients. These data support the hypothesis that ApoE may play a role in modulating NPC1 neuropathology.
尼曼-匹克病 C1 型（NPC1）是一种脂质贮积病，可导致进行性神经功能损伤。NPC1 的表型极其多样，在个体水平上可能受到其他遗传特征的影响。除 NPC1 蛋白的残余功能外，我们假设修饰基因（如经常在其他常染色体隐性疾病中观察到的那样）影响 NPC 表型。NPC1 的表型包括进行性痴呆，并且 NPC 病理学与阿尔茨海默病（AD）的病理学有一些重叠。因此，我们在一组 NPC1 患者中检查了载脂蛋白 E（ApoE）和微管相关蛋白 tau（MAPT）的多态性，这些患者具有特征明确的纵向疾病进展。尽管我们没有发现疾病严重程度与 tau 多态性之间的任何相关性，但我们发现 ApoE 多态性与表型严重程度之间存在显著关联。具体来说，在 NPC1 患者的这一组中，ApoE4 和 ApoE2 等位基因分别与疾病严重程度的增加和降低相关。这些数据支持了 ApoE 可能在调节 NPC1 神经病理学中发挥作用的假设。
