@article{10902/6232,
year = {2010},
url = {http://hdl.handle.net/10902/6232},
abstract = {Aberrant cholesterol metabolism has been implicated in Alzheimer´s disease (AD). Recent findings have suggested an interaction of Niemann-Pick C1 (NPC1) and ATP-binding cassette transporter A1 (ABCA1) proteins in intracellular cholesterol transport and in maintaining cell cholesterol balance. Underexpression of NPC1 in concert with underexpression of ABCA1 would result in increased cholesterol accumulation and increased AD risk. We examined a functional polymorphism in the ABCA1 promoter region (−477, rs2422493), and four NPC1 polymorphisms in exon 6 (rs18050810), intron 20 (rs4800488), intron 22 (rs2236707), and intron 24 (rs2510344) capturing 85% of genetic variability in Hap Map CEU population, in a group of 631 Spanish AD patients and 731 controls. Subjects carrying both the ABCA1 (−477) TT genotype and the NPC1 (exon 6) GG genotype (OR = 1.89; 95% CI 1.04-3.41), NPC1 (intron 20) AA genotype (OR = 2.05; 95% CI 1.26-3.33), NPC1 (intron 22) AA genotype (OR = 2.05; 95% CI 1.18-3.58), or NPC1 (intron 24) GG genotype (OR = 1.89; 95% CI 1.16-3.07) had a higher risk of developing AD than subjects without these risk genotypes. Testing for epistatic interaction between genes in the pathway of cholesterol metabolism might be useful for predicting AD risk.},
publisher = {IOS Press},
publisher = {Journal of Alzheimer's Disease. 2010;21(2):619-25},
title = {Epistasis between intracellular cholesterol trafficking-related genes (NPC1 and ABCA1) and Alzheimer's disease risk},
author = {Rodríguez Rodríguez, Eloy Manuel and Vázquez Higuera, José Luis and Sánchez-Juan, Pascual and Mateo Fernández, José Ignacio and Pozueta, Ana and Martínez García, Ana and Frank García, Ana and Valdivieso Amate, Fernando and Berciano, José Ángel and Bullido, María Jesús and Combarros Pascual, Onofre},
}