Neurobiology of Aging 30 (2009) 2082–2083
Negative results
Association study of the HLA-A2 allele in Italian Alzheimer
disease patients
Franca Rosa Guerini
a,∗
, Elena Calabrese
b
, Cristina Agliardi
a
, Milena Zanzottera
a
,
Massimo Franceschi
c
, Luigi Maria Edoardo Grimaldi
d
,
Raffaello Nemni
b,e
, Pasquale Ferrante
e
a
Laboratory of Molecular Medicine and Biotechnology, Don C. Gnocchi Foundation IRCCS, Milan, Italy
b
Department of Neurorehabilitation, Don C. Gnocchi Foundation IRCCS, Milan, Italy
c
Department of Neurology, IRCCS Multimedica, Santa Maria, Castellanza, Varese, Italy
d
Department of Neurology, Fondazione Istituto San Raffaele “G. Giglio” di Cefal` u, Italy
e
Department of Biomedical Science and Technology, University of Milan, Italy
Received 6 August 2007; received in revised form 30 January 2008; accepted 10 February 2008
Available online 21 March 2008
Abstract
Association of the A2 allele of the human leukocyte antigen (HLA) with Alzheimer disease (AD) is still controversial. The authors evaluated
HLA-A2 association with AD in 173 Italian AD patients, considering also the possible interaction with APOE pattern, age of onset and gender.
No evidence of any association was found.
© 2008 Elsevier Inc. All rights reserved.
Keywords: Alzheimer disease; Human leukocyte antigen; APOE
1. Introduction
The association between Alzheimer disease (AD) and
the A2 locus of the major histocompatiblity complex in
humans (HLA), is still controversial (Candore et al., 2004)
Significant results have been reported when AD patients
were subgrouped according to age at onset (Payami et al.,
1997; Listi et al., 2006), APOE interaction (Ballerini et al.,
1999), gender and family history (Harris et al., 2000). In one
case HLA-A2 homozygosity association with AD suscep-
tibility was suggested (Zareparsi et al., 2002). Conversely,
other studies excluded any correlation between HLA-A2
and AD (Nourhashemi et al., 2003; Araria-Goumidi et al.,
2002). We studied HLA-A2 distribution among Italian AD
∗
Corresponding author at: Laboratory of Molecular Medicine and
Biotechnology, IRCCS S. Maria Nascente, Don Gnocchi Foundation, Via
Capecelatro 66, 20148, Milan, Italy. Tel.: +39 02 40308376;
fax: +39 02 40308438.
E-mail address: fguerini@dongnocchi.it (F.R. Guerini).
patients and healthy controls (HC), taking into account the
possible interaction with APOE pattern, age at onset and
gender.
2. Results and conclusions
APOE and HLA-A2 genotype distribution were anal-
ysed in 173 AD patients and 258 sex- and age-matched
healthy controls (Table 1). Both the polymorphisms were in
Hardy–Weinberg equilibrium in HC group. Twenty patients
had a familial history of AD. Since no difference was reported
in comparison with sporadic AD subjects, the familial cases
were evaluated with all the other patients.
No significant difference was observed in HLA-A2 fre-
quency between AD patients and HC following stratification
according to gender and age at onset of disease, as shown
in Table 1. A lower frequency of HLA-A2 allele was found
in female late onset AD (LO-AD) patients (0.29) both than
female early onset AD (EO-AD) (0.45), female HC (0.48) and
0197-4580/$ – see front matter © 2008 Elsevier Inc. All rights reserved.
doi:10.1016/j.neurobiolaging.2008.02.001