Chromosome 9p21.3 genotype is associated with vascular dementia and Alzheimer's disease.
Vascular risk factors have been implicated in the pathogenesis of vascular dementia and Alzheimer's disease. The identification of a novel vascular disease susceptibility locus at 9p21.3 has recently generated great interest. In the present study, we sought to determine whether a common genetic variant (tagged by rs1333049, G/C) in the 9p21.3 locus-that has been previously linked to an increased vascular risk-might influence the susceptibility to vascular dementia (VaD) and late-onset Alzheimer's disease (LOAD). A cohort of 200 VaD patients, 407 LOAD patients and 405 cognitively healthy controls were genotyped for rs1333049 using a fluorogenic 5' nuclease assay. The frequency of the C allele of rs1333049 was significantly higher in VaD (62.2%, P=0.005) and LOAD (60.7%, P=0.004) patients than in controls (53.6%). After adjustment for the APOE ε4 carrier status and other vascular risk factors, the C allele of rs1333049 remained significantly associated with both VaD (OR 1.31, 95% CI 1.07-1.77, P<0.01) and LOAD (OR 1.28, 95% CI 1.04-1.55, P<0.01). Altogether, our data indicate for the first time that the C allele of rs1333049 in the vascular disease susceptibility locus is associated with VaD and LOAD, independent of traditional risk factors and the APOE ε4 genotype.
Emanuele
Enzo
E
Department of Health Sciences, Section of Psychiatry, University of Pavia, Via Bassi 21, Pavia, Italy. enzo.em@libero.it
Lista
Simone
S
Ghidoni
Roberta
R
Binetti
Giuliano
G
Cereda
Cristina
C
Benussi
Luisa
L
Maletta
Raffaele
R
Bruni
Amalia C
AC
Politi
Pierluigi
P
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D015331:Cohort Studies; D015140:Dementia, Vascular / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors