How to Cite this Article: Fu R, Yanjanin NM, Elrick MJ, Ware C, Lieberman AP, Porter FD. 2012. Apolipoprotein E genotype and neurological disease onset in Niemann–Pick disease, type C1. Am J Med Genet Part A 158A: 2775–2780.
Apolipoprotein E genotype and neurological disease onset in Niemann–Pick disease, type C1†
Article first published online: 28 SEP 2012
Copyright © 2012 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Special Issue: SPECIAL ISSUE: GROWTH CHARTS IN GENETIC SYNDROMES
Volume 158A, Issue 11, pages 2775–2780, November 2012
How to Cite
Fu, R., Yanjanin, N. M., Elrick, M. J., Ware, C., Lieberman, A. P. and Porter, F. D. (2012), Apolipoprotein E genotype and neurological disease onset in Niemann–Pick disease, type C1. Am. J. Med. Genet., 158A: 2775–2780. doi: 10.1002/ajmg.a.35395
- Issue published online: 17 OCT 2012
- Article first published online: 28 SEP 2012
- Manuscript Accepted: 3 MAR 2012
- Manuscript Received: 1 AUG 2011
- NIH. Grant Numbers: NS063967, NS065662
- neurodegenerative disease;
- lysosomal storage disease;
- apolipoprotein E;
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. © 2012 Wiley Periodicals, Inc.