HECTD2, a candidate susceptibility gene for Alzheimer's disease on 10q.
BACKGROUND
Late onset Alzheimer's disease (LOAD) is a neurodegenerative disorder characterised by the deposition of amyloid plaques and neurofibrillary tangles in the brain and is the major cause of dementia. Multiple genetic loci, including 10q, have been implicated in LOAD but to date, with the exception of APOE, the underlying genes have not been identified. HECTD2 maps to 10q and has been implicated in susceptibility to human prion diseases which are also neurodegenerative conditions associated with accumulation of misfolded host proteins. In this study we test whether the HECTD2 susceptibility allele seen in prion disease is also implicated in LOAD.


METHODS
DNA from 320 individuals with Alzheimer's disease and 601 controls were genotyped for a HECTD2 intronic tagging SNP, rs12249854 (A/T). Groups were further analysed following stratification by APOE genotype.


RESULTS
The rs12249854 minor allele (A) frequency was higher (5.8%) in the Alzheimer's disease group as compared to the controls (3.9%), however, this was not statistically significant (P = 0.0668). No significant difference was seen in minor allele frequency in the presence or absence of the APOE epsilon4 allele.


CONCLUSIONS
The common haplotypes of HECTD2, tagged by rs12249854, are not associated with susceptibility to LOAD.
Lloyd
Sarah E
SE
MRC Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK. s.lloyd@prion.ucl.ac.uk
Rossor
Martin
M
Fox
Nick
N
Mead
Simon
S
Collinge
John
J
D000293:Adolescent; D000328:Adult; D000544:Alzheimer Disease / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D002879:Chromosomes, Human, Pair 10; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
D001057:Apolipoproteins E; C544073:HECTD2 protein, human; D044767:Ubiquitin-Protein Ligases