APOE promoter polymorphisms and dementia in the elderly.
Previous observations suggest a contribution of two APOE promoter polymorphisms (-219 G/T and -491 A/T) in dementia. From two independent populations of elderly (mean age of 84 and 85 years old, respectively), we observed that subjects bearing the -219T allele were at increased risk of dementia (OR = 1.9 (95% CI, 1.3-2.8), P = 0.0003) or AD (OR = 2.0 (95% CI, 1.2-3.4), P < 0.008). Conversely, the -491 A/T variant was not associated with this risk of dementia in the elderly, as previously described. Haplotype estimations including the two promoter and the coding APOE polymorphisms indicated that the -491A/-219T/4 haplotype was at risk for the development of dementia (OR = 3.5 (95% CI, 2.5-5.0), P < 0.0001), whereas the -491A/-219G/4 haplotype was not (OR = 1.1 (95% CI, 0.6-2.1)). Similar results were observed when restricted to Alzheimer's disease. In conclusion, these data indicate that the -219 G/T polymorphism is a genetic determinant of dementia in the elderly, independently of the 4 allele.
Lambert
Jean-Charles
JC
INSERM U508, Institut Pasteur de Lille, 1 rue du professeur Calmette, BP 245, 59019 Lille Cedex, France.
Berr
Claudine
C
Cottel
Dominique
D
Amouyel
Philippe
P
Helbecque
Nicole
N
D000368:Aged; D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000235:genetics*; D016022:Case-Control Studies; D003704:Dementia / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012306:Risk; D044465:White People / Q000235:genetics
D001057:Apolipoproteins E