Association between the HLA-A2 allele and Alzheimer disease
F. Listì, G. Candore, C.R. Balistreri, S. Vasto, M.P. Grimaldi, G. Colonna-Romano, A. Giacalone, V. Orlando, D. Lio, C. Franceschi, C. Caruso
Gruppo di Studio sull'Immunosenescenza, Dipartimento di Biopatologia e Metodologie Biomediche, Università di Palermo, Corso Tukory 211, 90134 Palermo
The progressive neurodegenerative inflammatory age-related disease,
Alzheimers disease (AD), is the most common cause of dementia in the
elderly. Several factors, genetic and environmental, are involved in
the onset of AD. Epidemiological data suggest that some genetic
determinants of AD might reside in those polymorphisms for the immune
system genes that regulate immune inflammatory responses, such as the
Major Histocompatibility Complex (MHC). Therefore, MHC polymorphisms
have been the focus of a large number of AD association studies. A
possible association of HLA-A2 alleles with increased susceptibility to
AD has been the subject of debate for more than 20 years, even if the
results of these studies, in the various populations, are discordant.
Thus, to gain insight in this matter, we have valuated if HLA-A2
allele is associated with AD in a homogeneous populations of Italian
patients with sporadic AD. To this aim, we have analysed the
distribution of HLA-A2 allele in patients with AD and controls, by
PCR-SSP. Our results demonstrate a significant difference in the
frequency of HLA-A2 allele between patients with AD and controls (46%
vs. 38%). Then, our results confirm a positive role of HLA-A2 allele in
the risk of onset of AD. Some of observed discrepancies may reflect the
clinical or genetic heterogeneity of the populations studied or be due
to methodological biases. Besides, if external agents such as viruses
as suggested, play a role, these might be different in different
population leading to different associations. However, in particular
for discrepant results concerning HLA-A2, it has to be taken into
account that there are many molecular HLA-A2 subtypes with different
frequencies in different populations. So, further studies should
include molecular typing of HLA-A2 subtypes.
Key words:
AD, HLA, IMMUNE RESPONSE
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