Apolipoprotein E genotypic frequencies among Down syndrome patients imply early unsuccessful aging for ApoE4 carriers.
Down syndrome (DS) might be considered a model for unsuccessful and early aging, possibly accelerated for those who carry the APOE4 allele associated with common age-related diseases, e.g., Alzheimer's disease and a poor prognosis after acute myocardial infarction, causing lower ApoE4 frequencies among the very old in general populations. We compared ApoE genotypic frequencies found for healthy adults (n = 211, age < 40; n = 79, ages 70-79; n = 71, ages > 90) to those found for DS patients (n = 106, mean age 9 years), all living in western Sicily. We found that the frequency of the ApoE23 genotype increased with age among the healthy adults (8.5%, 6.4%, 19.7%; p = 0.024) while ApoE34 frequency decreased (16.1%, 12.6%, 4.1%; p = 0.012). DS patients had APOE34 genotypic frequencies very similar to those found in septuagenarians (9%; p = 0.005). Analyzing results according to surviving rate of persons with DS, an age-related reduction of ApoE3/4 genotype frequency was found comparing =5 years old to >5 years old DS subjects. These results highlight DS as a model to understand the role of APOE4 allele in unsuccessful ageing considering that a number of proinflammatory supernumerary genes (Cu/Zn superoxide dismutase, Ets-2 transcription factors, Down syndrome critical region 1, stress-inducible factor, interferon-alpha receptor and the amyloid precursor protein) are located on chromosome 21 and are implied in the pathologic processes of DS.
Forte
Giusi I
GI
Gruppo di studio sull'Immunosenescenza, Dipartimento di Biopatologia e Metodologie Biomediche, Università Palermo, Palermo, Italy.
Piccione
Maria
M
Scola
Letizia
L
Crivello
Antonino
A
Galfano
Cristina
C
Corsi
Massimiliano M
MM
Chiappelli
Martina
M
Candore
Giuseppina
G
Giuffrè
Mario
M
Verna
Roberto
R
Licastro
Federico
F
Corsello
Giovanni
G
Caruso
Calogero
C
Lio
Domenico
D
D000293:Adolescent; D000328:Adult; D000375:Aging / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics* / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D002891:Chromosomes, Human, Pair 21; D004314:Down Syndrome / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D011379:Prognosis; D017422:Sequence Analysis, DNA
D053327:Apolipoprotein E4