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

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.