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Substantial Linkage Disequilibrium Across the Dihydrolipoyl Succinyltransferase Gene Region Without Alzheimer's Disease Association

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Abstract

Association of the candidate gene DLST with late-onset Alzheimer's disease (LOAD) risk has been suggested on the basis of case-control studies. This gene, located on chromosome 24q24.3, encodes a subunit of a mitochondrial component known to be defective in AD, the α-ketoglutarate dehydrogenase complex. Positive reports have correlated different DLST alleles with LOAD, whereas other groups have failed to find any significant association. We therefore reexamined the association of DLST and LOAD in a more ethnically homogeneous series using three additional single nucleotide polymorphisms (SNP) located within or closely flanking either end of the DLST gene. Pairwise analysis of these SNPs indicated there was strong linkage disequilibrium across the DLST locus. Analysis of complex genotypes or haplotypes based upon all five SNP loci failed to identify a LOAD risk allele, suggesting that further studies of DLST in relation to AD are not warranted.

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Authors and Affiliations

  1. Burke Medical Research Institute, White Plains, New York

    Abraham M. Brown, Hsinhwa Lee, Michael Caudy & John P. Blass

  2. Department of Biochemistry, Weill Medical College of Cornell University, New York, New York

    Abraham M. Brown

  3. Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, New York

    Michael Caudy & John P. Blass

  4. Department of Medicine, Weill Medical College of Cornell University, New York, New York

    John P. Blass

  5. Laboratory of Statistical Genetics, Rockefeller University, New York, New York

    Derek Gordon

  6. Department of Psychiatry, Mount Sinai School of Medicine, Bronx Veterans Administration Medical Center, Bronx, New York

    Vahram Haroutunian

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Correspondence to Abraham M. Brown.

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Brown, A.M., Gordon, D., Lee, H. et al. Substantial Linkage Disequilibrium Across the Dihydrolipoyl Succinyltransferase Gene Region Without Alzheimer's Disease Association. Neurochem Res 29, 629–635 (2004). https://doi.org/10.1023/B:NERE.0000014833.54481.1d

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