Replication of the association of HLA-B7 with Alzheimer's disease: a role for homozygosity?

doi:10.1186/1742-2094-3-33

Journal of Neuroinflammation

Volume 3

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Lehmann DJ
Barnardo MC
Fuggle S
Quiroga I
Sutherland A
Warden DR
Barnetson L
Horton R
Beck S
Smith AD

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Lehmann DJ
Barnardo MC
Fuggle S
Quiroga I
Sutherland A
Warden DR
Barnetson L
Horton R
Beck S
Smith AD
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Research

Replication of the association of HLA-B7 with Alzheimer's disease: a role for homozygosity?

Donald J Lehmann¹^,2 , Martin CNM Barnardo³^,4 , Susan Fuggle³^,4 , Isabel Quiroga³^,4 , Andrew Sutherland³^,4 , Donald R Warden¹^,2 , Lin Barnetson¹ , Roger Horton⁵ , Stephan Beck⁵ and A David Smith¹^,2

¹The Oxford Project to Investigate Memory and Ageing (OPTIMA), University Department of Pharmacology & Radcliffe Infirmary, Oxford, UK

²Oxford Centre for Gene Function, University Department of Physiology, Anatomy & Genetics, Parks Rd, Oxford OX1 3PT, UK

³Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK

⁴Oxford Transplant Centre, Churchill Hospital, Oxford OX3 7LJ, UK

⁵Immunogenomics Laboratory, Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK

author email corresponding author email

Journal of Neuroinflammation 2006, 3:33doi:10.1186/1742-2094-3-33


Published:	18 December 2006

Abstract

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 ε4 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.

Conclusion

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.