Gender-specific association of ATP-binding cassette transporter 1 (ABCA1) polymorphisms with the risk of late-onset Alzheimer's disease

Neurobiol Aging. 2007 Jun;28(6):856-62. doi: 10.1016/j.neurobiolaging.2006.04.005. Epub 2006 May 24.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters / genetics*
  • Adaptor Proteins, Signal Transducing
  • Aged
  • Alzheimer Disease / genetics*
  • Apolipoprotein E4 / genetics
  • Arginine / genetics
  • Autophagy-Related Proteins
  • Carrier Proteins / genetics
  • Cell Cycle Proteins / genetics
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Linkage Disequilibrium
  • Logistic Models
  • Lysine / genetics
  • Male
  • Polymorphism, Genetic / genetics*
  • Sex Characteristics*


  • ABCA1 protein, human
  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters
  • Adaptor Proteins, Signal Transducing
  • Apolipoprotein E4
  • Autophagy-Related Proteins
  • Carrier Proteins
  • Cell Cycle Proteins
  • UBQLN1 protein, human
  • Arginine
  • Lysine