Chromosome 9p21.3 genotype is associated with vascular dementia and Alzheimer's disease

• Published in: Neurobiology of aging 2011-07, Vol.32 (7), p.1231-1235
• Main Authors: Emanuele, Enzo, Lista, Simone, Ghidoni, Roberta, Binetti, Giuliano, Cereda, Cristina, Benussi, Luisa, Maletta, Raffaele, Bruni, Amalia C, Politi, Pierluigi
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Alleles; Alzheimer Disease - epidemiology; Alzheimer Disease - genetics; Alzheimer Disease - physiopathology; Alzheimer's disease; Biological and medical sciences; Chromosomes, Human, Pair 9 - genetics; Cohort Studies; Dementia, Vascular - epidemiology; Dementia, Vascular - genetics; Dementia, Vascular - physiopathology; Development. Senescence. Regeneration. Transplantation; Female; Fundamental and applied biological sciences. Psychology; Genetic Predisposition to Disease - epidemiology; Genetic Predisposition to Disease - genetics; Genotype; Humans; Internal Medicine; Male; Medical sciences; Neurology; Polymorphism; Polymorphism, Single Nucleotide - genetics; Risk Factors; Vascular dementia; Vascular diseases and vascular malformations of the nervous system; Vertebrates: nervous system and sense organs
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2009.07.003

Abstract 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.