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 14q24.3, encodes a subunit of a mitochondrial component known to be defective in AD, the alpha-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.
Brown
Abraham M
AM
Dementia Research Service, Burke Medical Research Institute, 785 Mamaroneck Avenue, White Plains, New York 10605, USA. ambrown@med.cornell.edu
Gordon
Derek
D
Lee
Hsinhwa
H
Caudy
Michael
M
Haroutunian
Vahram
V
Blass
John P
JP
D000217:Acyltransferases / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology* / Q000235:genetics*; D001483:Base Sequence; D001921:Brain / Q000201:enzymology*; D017931:DNA Primers; D005787:Gene Frequency; D005819:Genetic Markers; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics*; D008875:Middle Aged; D012016:Reference Values; D012044:Regression Analysis
D017931:DNA Primers; D005819:Genetic Markers; D000217:Acyltransferases; C021515:dihydrolipoamide succinyltransferase