Gender-specific association of ATP-binding cassette transporter I (ABCA1) polymorphisms with the risk of late-onset Alzheimer's disease

被引:60
作者
Sundar, Purnima Desai
Feingold, Eleanor
Minster, Ryan L.
DeKosky, Steven T.
Kamboh, M. Ilyas [1 ]
机构
[1] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA
[2] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15261 USA
[3] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15261 USA
关键词
Alzheimer's disease; ABCA1; polymorphism;
D O I
10.1016/j.neurobiolaging.2006.04.005
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder caused by a complex interaction of genetic and environmental factors. Increasing evidence highlights a potential role for cholesterol in the pathophysiology of AD. The ABCA1 gene, located in close vicinity to the 9q linkage peaks identified by genome-wide AD linkage studies., plays an important role in cellular cholesterol efflux, and is likely a good candidate gene. However, results from published genetic association studies between ABCA1 and AD are ambiguous. In the present study, we examined the role of two ABCA1 polymorphisms, R219K (rs2230806) and G-17C (rs2740483) in modifying the risk of late-onset AD (LOAD) in a large American white cohort of 992 AD cases and 699 controls. We observed significant gender x R219K interaction (p=0.00008). Female carriers of the 219K allele showed a 1.75-fold increased risk of developing AD compared to non-219K carrier females (95% CI 1.34-2.29; p = 0.00004). The overall two-site haplotype distribution was also significant between female AD cases and controls (p =0.017). The risk associated with the R219K polymorphism was independent of the recently reported significant association in the ubiquilin (UBQLN1) gene in this region on chromosome 9q. Our data suggest a gender-specific and APOE and UBQLN1 independent association between the ABCA1/R219K polymorphism and LOAD. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:856 / 862
页数:7
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