Association of the dihydrolipoamide dehydrogenase gene with Alzheimer's disease in an Ashkenazi Jewish population. Academic Article uri icon

Overview

abstract

  • Abundant biochemical evidence links deficient activity of mitochondrial alpha-ketoglutarate dehydrogenase with neuropathologically confirmed Alzheimer's disease (AD). Reduced alpha-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.

publication date

  • November 15, 2004

Research

keywords

  • Alzheimer Disease
  • Dihydrolipoamide Dehydrogenase
  • Jews

Identity

Scopus Document Identifier

  • 7644243802

Digital Object Identifier (DOI)

  • 10.1002/ajmg.b.30008

PubMed ID

  • 15389771

Additional Document Info

volume

  • 131B

issue

  • 1