Please cite this article as follows: Heshmati Y, Mirabzadeh A, Feizzade G, Gilanipour M, Etminan MR, Khoram Khorshid HR, Kamali K, Fakhri M, Moghimi N, Najmabadi H, Ohadi M. 2009. A Novel Polymorphic Purine Complex at the 1.5 kb Upstream Region of the Human Caveolin-1 Gene and Risk of Alzheimer's Disease; Extra-Short Alleles and Accumulated Allele Homozygosity. Am J Med Genet Part B 150B:248–253.
A novel polymorphic purine complex at the 1.5 kb upstream region of the human caveolin-1 gene and risk of Alzheimer's disease; Extra-short alleles and accumulated allele homozygosity†
Article first published online: 16 JUN 2008
Copyright © 2008 Wiley-Liss, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume 150B, Issue 2, pages 248–253, 5 March 2009
How to Cite
Heshmati, Y., Mirabzadeh, A., Feizzade, G., Gilanipour, M., Etminan, M.R., Khoram Khorshid, H.R., Kamali, K., Fakhri, M., Moghimi, N., Najmabadi, H. and Ohadi, M. (2009), A novel polymorphic purine complex at the 1.5 kb upstream region of the human caveolin-1 gene and risk of Alzheimer's disease; Extra-short alleles and accumulated allele homozygosity. Am. J. Med. Genet., 150B: 248–253. doi: 10.1002/ajmg.b.30805
- Issue published online: 19 FEB 2009
- Article first published online: 16 JUN 2008
- Manuscript Accepted: 7 MAY 2008
- Manuscript Received: 15 JAN 2008
- Alzheimer's disease;
Crucial interaction of caveolin-1 (CAV1) with β- and γ-secretases, and aberrant expression of the gene encoding this protein in Alzheimer's disease (AD) support a role for CAV1 in the pathophysiology of this disease. We report a novel polymorphic purine complex stretching ∼150 bp of genomic DNA at the 1.5 kb upstream region of the human CAV1 gene, alleles and genotypes of which are associated with sporadic late-onset AD. Extra-short alleles were observed in the case group that were absent in the control subjects. Remarkably, 63% of these alleles were observed to be homozygous in length, forming 23.7% of the homozygote length compartment in the AD cases (χ2 = 19.08, df = 1, P < 0.000007). Increased homozygosity for length was also observed at this region in the Alzheimer's cases, for the allele lengths shared by the case and control groups [(χ2 = 30.75, df = 1, P < 0.0000000, OR = 4.54, CI 95% (2.56–8.3)]. This region 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 this complex sequence on the expression of CAV1, and the related mechanisms in the pathophysiology of AD remain to be clarified. © 2008 Wiley-Liss, Inc.