Replication of the association of HLA-B7 with Alzheimer's disease: a role for homozygosity?
BACKGROUND
There are reasons to expect an association with Alzheimer's disease (AD) within the HLA region. The HLA-B & C genes have, however, been relatively understudied. A geographically specific association with HLA-B7 & HLA-Cw*0702 had been suggested by our previous, small study.


METHODS
We studied the HLA-B & C alleles in 196 cases of 'definite' or 'probable' AD and 199 elderly controls of the OPTIMA cohort, the largest full study of these alleles in AD to date.


RESULTS
We replicated the association of HLA-B7 with AD (overall, adjusted odds ratio = 2.3, 95% confidence interval = 1.4-3.7, p = 0.001), but not the previously suggested interaction with the epsilon4 allele of apolipoprotein E. Results for HLA-Cw*0702, which is in tight linkage disequilibrium with HLA-B7, were consistent with those for the latter. Homozygotes of both alleles appeared to be at particularly high risk of AD.


CONCLUSIONS
HLA-B7 and HLA-Cw*0702 are associated with AD in the Oxford population. Because of the contradictions between cohorts in our previous study, we suggest that these results may be geographically specific. This might be because of differences between populations in the structure of linkage disequilibrium or in interactions with environmental, genetic or epigenetic factors. A much larger study will be needed to clarify the role of homozygosity of HLA alleles in AD risk.
Lehmann
Donald J
DJ
The Oxford Project to Investigate Memory and Ageing (OPTIMA), University Department of Pharmacology & Radcliffe Infirmary, Oxford, UK. donald.lehmann@pharm.ox.ac.uk
Barnardo
Martin C N M
MC
Fuggle
Susan
S
Quiroga
Isabel
I
Sutherland
Andrew
A
Warden
Donald R
DR
Barnetson
Lin
L
Horton
Roger
R
Beck
Stephan
S
Smith
A David
AD