The human caveolin 1 gene upstream purine complex and neurodegeneration—A common signature

Abstract The caveolin 1 gene ( CAV1 ) is over-expressed in experimental animal models of multiple sclerosis (MS). Increased expression of this gene has also been reported in the Alzheimer's disease (AD) brain. Loss of this gene, on the other hand, has recently been reported to be associated with neruodegeneration. We have recently reported skew in the homozygote haplotypes of the human CAV1 gene − 1.5 kb upstream purine complex in patients afflicted with MS and late-onset AD vs. controls. In order to examine reproducibility of those findings, we sequenced the region in independent groups of MS patients (n = 120) and controls (n = 150). We report two novel extreme homozygote haplotypes at 86-bp and 142-bp in the patients vs. controls. The above haplotypes were also detected in the previously reported cases of late-onset AD. The range of homozygote haplotypes in the controls was detected at between 106-bp to 122-bp. Following pooling of the neurodegenerative (n = 486) and non-neurodegenerative (n = 610) subjects studied for the human CAV1 purine complex to date, twenty haplotypes were found to be homozygous in the neurodegenerative, and not in the control pool (p < 0.000001). Six overlapping haplotypes were detected in the MS and AD patients (p < 0.007), strengthening the role of this region as a common etiological factor in the pathophysiology of neurodegenerative disorders, possibly through inflammatory mechanisms. Those overlapping haplotypes contained motif lengths that were non-existent in the control homozygote pool. The CAV1 purine complex GGAA and GAAA motifs are binding sites for numerous inflammatory transcription factors including the Ets, STAT, and IRF family members. Further work on the functionality of this region will shed light on the downstream events to the disease-linked haplotypes.