Angiotensin converting enzyme insertion/deletion polymorphism in sporadic and familial Alzheimer's disease and longevity.
A recent, large meta-analysis has reproposed the role of the angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism as a risk factor for Alzheimer's disease (AD). To further investigate the proposed association and to better clarify the role of ACE as a risk factor for AD, we analyzed the genotype and allele frequency distribution of ACE I/D and apolipoprotein E (APOE) gene polymorphisms in 235 Italian patients with sporadic AD, 153 with familial AD (FAD), 192 healthy controls and 111 centenarians. Patients with AD were consecutively gathered from among the outpatients from the Neurology Department at the University of Florence. All 691 subjects were genotyped for ACE and APOE polymorphisms. There were no significant differences in ACE genotypes or allele frequencies in all the studied groups, even after stratification for APOE epsilon4 carrier status. Centenarians show the highest allele D frequency, although the value is not significant, thus suggesting a possible implication of the D allele as an epistatic allele that has pleiotropic age-dependent effects. In conclusion, our data suggest that the ACE allelic variant is not a susceptibility factor in sporadic and familial AD (FAD), nor does it mitigate the effect of the APOE epsilon4 allele in the risk of developing AD. Moreover, our data do not suggest a possible involvement of the D allele in longevity.
Nacmias
Benedetta
B
Department of Neurological and Psychiatric Sciences, University of Florence, Florence and Centro di Ricerca, Trasferimento e Alta Formazione DENOTHE, University of Florence, Viale Morgagni, 85, 50134 Firenze, Italy. nacmias@unifi.it
Bagnoli
Silvia
S
Tedde
Andrea
A
Cellini
Elena
E
Bessi
Valentina
V
Guarnieri
Biancamaria
B
Ortensi
Luigi
L
Piacentini
Silvia
S
Bracco
Laura
L
Sorbi
Sandro
S
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007558:Italy; D008136:Longevity / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017384:Sequence Deletion
D053327:Apolipoprotein E4; D007703:Peptidyl-Dipeptidase A