Extreme Alleles at the Human Caveolin 1 Gene Novel Purine Complex and Risk of Alzheimer’s Disease

Abstract

Caveolin-1 (CAV1) is the principal structural protein of caveolae membranes that are found in most cell types. Aberrant expression and mutation of this gene are associated with a wide range of disorders including neurodegenerative disorders and various cancers. We report a novel purine complex of three polymorphic motifs located at the enhancer region of the gene and risk of late-onset Alzheimer's disease. Extreme haplotypes with accumulated homozygosity for those haplotypes were observed in the Alzheimer's cases comparing with the controls (p< 0.000). Based on our findings, there is a window of haplotypes and haplotype lengths in the controls. Shorter and longer haplotypes were associated with Alzheimer's disease in our cases.

This purine complex contains GGAA and GAAA motifs, the consensus binding sites for the Ets and IRF family transcription factors, respectively, and is highly conserved in distantly-related non-human primates in respect with location and motif sequence. The effect of the extreme haplotypes in the expression of the gene and the pathophysiology of Alzheimer's disease remain to be clarified.