Association of the dihydrolipoamide dehydrogenase gene with Alzheimer's disease in an Ashkenazi Jewish population
Article first published online: 27 JUL 2004
Copyright © 2004 Wiley-Liss, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume 131B, Issue 1, pages 60–66, 15 November 2004
How to Cite
Brown, A. M., Gordon, D., Lee, H., Caudy, M., Hardy, J., Haroutunian, V. and Blass, J. P. (2004), Association of the dihydrolipoamide dehydrogenase gene with Alzheimer's disease in an Ashkenazi Jewish population. Am. J. Med. Genet., 131B: 60–66. doi: 10.1002/ajmg.b.30008
- Issue published online: 25 OCT 2004
- Article first published online: 27 JUL 2004
- Manuscript Accepted: 7 NOV 2003
- Manuscript Received: 2 JUL 2003
- NIH. Grant Number: P01-AG14930 (JPB), K01-HG00055 (DG), P01-AG02219 (VH), MH44292 (J. Ott).
- Winifred Masterson Burke Relief Foundation (AMB)
Abundant biochemical evidence links deficient activity of mitochondrial α-ketoglutarate dehydrogenase with neuropathologically confirmed Alzheimer's disease (AD). Reduced α-ketoglutarate dehydrogenase activity has also been associated with anti-mortem measures of clinical disability. One of the genes encoding this complex, namely, DLD, lies within a chromosome 7 region that is in linkage disequilibrium with AD. We therefore examined the hypothesis that variation in DLD is associated with AD risk. Denaturing HPLC was used to search for sequence variations in the coding and flanking regions of all exons of DLD, but no abundant variants that alter protein sequence were found. However, four common SNPs were identified and genotyped in a case-control series of 297 Caucasians from New York City, including 229 residents of a Jewish nursing home. Logistic regression analysis was performed for the four-locus DLD genotype, sex, and ApoE4 status to determine the association of these independent variables with AD. Significant associations with AD were observed for ApoE4 (P < 10−6) and sex combined with DLD genotype (P = 0.013). The association with the DLD genotypes appears only in the male population in both the Caucasian series (P = 0.0009, n = 83) and the Ashkenazi Jewish subseries (P = 0.017, n = 49). The DLD genotype appears to operate independently of APOE in conferring AD risk. © 2004 Wiley-Liss, Inc.